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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Expansion of CD26 positive fibroblast population promotes keloid progression

Background: Keloid is a skin fibrosis disease that characterised by invasive growth of fibroblasts and aberrant deposition of extracellular matrix. Studies indicated that keloid fibroblasts (KFs) is a class of ‘activated’ fibroblasts, which show accelerated proliferation and excessive extracellular matrix formation as compared with normal fibroblasts (NFs). However, the mechanism underlying keloid fibroblasts dysfunction is still unknown. Objective: To verify CD26 expression difference between KFs and NFs, and investigate the function of CD26 positive fibroblasts in keloid progression. Methods: KFs and NFs were isolated from Keloid tissues and normal skin tissues respectively. Flow cytometry was performed to isolate CD26+/CD26- fibroblasts from KFs and NFs. Proliferation of different fibroblasts were analyzed by CCK8 assay and Ki 67 straining. Profibrotic phenotype difference was detected by qRT-PCR, western blot, ELISA and immunofluorescence. Scratching experiment and transwell assay were used to assess invasion ability of CD26+/CD26- fibroblasts. Diprotin A was used as a CD26 inhibitor to further investigated the function of CD26 fibroblasts in keloid disease. Result: CD26 expression was increased in KFs, and the proportion of CD26+ fibroblasts was significantly increased in KFs. Cell viability analysis showed that CD26+ fibroblasts was more active in proliferation. Furthermore, the expression of profibrotic genes were increased in CD26+ fibroblasts, including TGF-β1, IGF-1, IL6, collagen 1, collagen 3 and fibronectin. And meanwhile, CD26+ fibroblasts showed stronger invasion ability as compared to CD26- fibroblasts. Moreover, Diprotin A significantly suppressed proliferation and extracellular matrix secretion of CD26+ fibroblasts isolated from keloid tissues. Conclusion: Our findings suggest that CD26+ fibroblasts possess proliferation advantage in compare to CD26- fibroblasts, and the advantage caused expansion of CD26 positive fibroblast population promotes keloid progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Heterogeneous response of cancer-associated fibroblasts to the glucose deprivation through mitochondrial calcium uniporter

Highlights: • CAFs from a tumor mass are heterogeneous under the glucose deficient condition. • CAFs survive under glucose deficient condition by activation of TGF-β and calcium. • Calcium influx to mitochondria is critical for survival of glucose-deficient CAFs. • MCU in CAFs could be a feasible target for the development of anticancer drugs. Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have distinct features from normal fibroblasts (NFs). However, the discriminative nature of heterogeneous CAFs under glucose starvation remains unknown. In this study, we investigated the changes in the mitochondrial calcium concentration and relevant intracellular machinery in CAFs under glucose-deficient conditions. Xenografted tumor masses were dissected into multiple pieces and subjected to the CAF isolation using magnetically activated cell sorting (MACS). NFs were separated from the normal lung and skin. Under glucose starvation, CAFs from the tumor mass exhibited heterogeneity in cell proliferation, ATP production and calcium concentration. Compared to NFs, mitochondrial calcium concentration was significantly higher in glucose-starved CAFs with upregulation of mitochondrial calcium uniporter (MCU) that led to enhancement of ATP production and cell growth. Intriguingly, treatment of glucose-starved CAFs with oligomycin increased apoptosis by disrupted calcium homeostasis following overactivation of the mPTP. Moreover, oligomycin-induced apoptosis was mitigated by calcium chelation. This study demonstrated that the discriminative calcium influx to mitochondria through MCU coordinated cell growth and apoptosis in glucose-starved CAFs but not in NFs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Unveiling Spatial and Temporal Dynamics of Plasmon-Enhanced Localized Fields in Metallic Nanoframes through Ultrafast Electron Microscopy

Plasmonic nanomaterials, particularly noble metal nanoframes (NFs), are important for applications such as catalysis, biosensing, and energy harvesting due to their ability to enhance localized electric fields and atomic efficiency via localized surface plasmon resonance (LSPR). Yet the fundamental structure-function relationships and plasmonic dynamics of the NFS are difficult to study experimentally and thus far rely predominately on computational methodologies, limiting their utilization. This study leverages the capabilities of ultrafast electron microscopy (UEM), specifically photon-induced near-field electron microscopy (PINEM), to probe the light-matter interactions within plasmonic NF structures. Here, the effects of shape, size, and plasmonic coupling of Pt@Au core-shell NFs on spatial and temporal characteristics of plasmon-enhanced localized electric fields are explored. Importantly, time-resolved PINEM analysis reveals that the plasmonic fields around hexagonal NF prisms exhibit a spatially dependent excitation and decay rate, indicating a nuanced interplay between the spatial geometry of the NF and the temporal evolution of the localized electric field. These results and observations uncover nanophotonic energy transfer dynamics in NFs and highlight their potential for applications in biosensing and photocatalysis.

Plasmonics↗
DOE OSTI2014

Growth of vertically aligned α−MoO{sub 3} nanoflakes by using a facile PVD route

In this report, we synthesize vertically aligned molybdenum trioxide (α−MoO{sub 3}) nanoflakes (NFs) with high aspect ratio (height/thickness >15) on the cobalt coated glass substrates by the plasma assisted sublimation process, employing Mo metal strip as a sublimation source. The effect of substrate temperature, nature of substrate as well as the geometry of the sublimation source (Mo-strip) have been investigated on the morphological, structural and optical properties of the grown NFs, keeping plasma parameters as fixed. The surface morphology, crystalline structure and optical properties of MoO{sub 3} NFs have been studied systematically by using scanning electron microscope (SEM), transmission electron microscope (TEM) with selected area electron diffraction (SAED), X-ray diffractometer, and IR- spectroscopy. The experimental observations endorse that the characteristics of MoO{sub 3} NFs are strongly depend on substrate temperature, substrate nature as well as geometry of Mo-strip. All the observed results are well in consonance with each other.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2013

COMPARISON OF RESULTS FOR QUARTER 2 SURFACE WATER SPLIT SAMPLES COLLECTED AT THE NUCLEAR FUEL SERVICES SITE, ERWIN, TENNESSEE

Oak Ridge Associated Universities (ORAU), under the Oak Ridge Institute for Science and Education (ORISE) contract, collected split surface water samples with Nuclear Fuel Services (NFS) representatives on November 15, 2012. Representatives from the U.S. Nuclear Regulatory Commission and Tennessee Department of Environment and Conservation were also in attendance. Samples were collected at four surface water stations, as required in the approved Request for Technical Assistance number 11-018. These stations included Nolichucky River upstream (NRU), Nolichucky River downstream (NRD), Martin Creek upstream (MCU), and Martin Creek downstream (MCD). Both ORAU and NFS performed gross alpha and gross beta analyses, and the results are compared using the duplicate error ratio (DER), also known as the normalized absolute difference. A DER {<=} 3 indicates that, at a 99% confidence interval, split sample results do not differ significantly when compared to their respective one standard deviation (sigma) uncertainty (ANSI N42.22). The NFS split sample report does not specify the confidence level of reported uncertainties (NFS 2012). Therefore, standard two sigma reporting is assumed and uncertainty values were divided by 1.96. In conclusion, all DER values were less than 3 and results are consistent with low (e.g., background) concentrations.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1994

National facilities study. Volume 3: Mission and requirements model report

The National Facility Study (NFS) was initiated in 1992 by Daniel S. Goldin, Administrator of NASA as an initiative to develop a comprehensive and integrated long-term plan for future facilities. The resulting, multi-agency NFS consisted of three Task Groups: Aeronautics, Space Operations, and Space Research and Development (R&D) Task Groups. A fourth group, the Engineering and Cost Analysis Task Group, was subsequently added to provide cross-cutting functions, such as assuring consistency in developing an inventory of space facilities. Space facilities decisions require an assessment of current and future needs. Therefore, the two task groups dealing with space developed a consistent model of future space mission programs, operations and R&D. The model is a middle ground baseline constructed for NFS analytical purposes with excursions to cover potential space program strategies. The model includes three major sectors: DOD, civilian government, and commercial space. The model spans the next 30 years because of the long lead times associated with facilities development and usage. This document, Volume 3 of the final NFS report, is organized along the following lines: Executive Summary -- provides a summary view of the 30-year mission forecast and requirements baseline, an overview of excursions from that baseline that were studied, and organization of the report; Introduction -- provides discussions of the methodology used in this analysis; Baseline Model -- provides the mission and requirements model baseline developed for Space Operations and Space R&D analyses; Excursions from the baseline -- reviews the details of variations or 'excursions' that were developed to test the future program projections captured in the baseline; and a Glossary of Acronyms.

Source record↗
NASA NTRS1994

Space facilities: Meeting future needs for research, development, and operations

The National Facilities Study (NFS) represents an interagency effort to develop a comprehensive and integrated long-term plan for world-class aeronautical and space facilities that meet current and projected needs for commercial and government aerospace research and development and space operations. At the request of NASA and the DOD, the National Research Council's Committee on Space Facilities has reviewed the space related findings of the NFS. The inventory of more than 2800 facilities will be an important resource, especially if it continues to be updated and maintained as the NFS report recommends. The data in the inventory provide the basis for a much better understanding of the resources available in the national facilities infrastructure, as well as extensive information on which to base rational decisions about current and future facilities needs. The working groups have used the inventory data and other information to make a set of recommendations that include estimates of cast savings and steps for implementation. While it is natural that the NFS focused on cost reduction and consolidations, such a study is most useful to future planning if it gives equal weight to guiding the direction of future facilities needed to satisfy legitimate national aspirations. Even in the context of cost reduction through facilities closures and consolidations, the study is timid about recognizing and proposing program changes and realignments of roles and missions to capture what could be significant savings and increased effectiveness. The recommendations of the Committee on Space Facilities are driven by the clear need to be more realistic and precise both in recognizing current incentives and disincentives in the aerospace industry and in forecasting future conditions for U.S. space activities.

Source record↗
DOE OSTI2012

Petascale Data Storage Institute (Final Report)

pNFS is an extension to NFSv4 that helps clients overcome NFS scalability and performance barriers. Like NFS, pNFS is a client/server protocol implemented with secure and reliable remote procedure calls. pNFS departs from conventional NFS by allowing clients to access storage directly and in parallel. This helps overcome server bottlenecks inherent to NAS access methods. Making pNFS available to petascale researchers required coordinated progress in several dimensions, a confluence of multiple processes that took nearly ten years. The protocol had to be specified and published by the IETF. Nascent implementations had to track changes in the draft specification, changes in the Linux kernel, and interoperate with one another. The process by which modifications are accepted into the Linux kernel by maintainers and developers (and ultimately by Linus Torvalds himself) itself required consensus and compromise. Finally, pNFS support needed to be provided by the major Linux distributors (Red Hat, SUSE, etc.) and storage vendors (Netapp, EMC, IBM, Microsoft, etc.) on both the engineering and product sides. The specification requirement was met in December 2008, when the IETF approved the NFSv4.1 specification, which incorporates pNFS and pNFS file layouts, as a Proposed Standard as well as the (separate) specifications of pNFS object and block layouts. Throughout the PDSI project, CITI was the key contributor to the Linux-based, open source implementation of NFSv4.1 and pNFS. Considerable effort was devoted to the process of refining the IETF specification, which underwent dozens of preliminary drafts, rebasing implementations to the latest Linux kernel, which itself changed quarterly, and to testing interoperability with other developers. At last, the Linux pNFS implementation was incorporated into the Linux mainline kernel, although this was achieved after the PDSI project ended.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2018

Rheological Properties of Poly(lactic acid) Solutions Added with Metal Oxide Nanoparticles for Electrospinning

Nanocomposites based on poly(lactic acid) (PLA) with antibacterial properties are of great potential interest as food packaging biomaterials. The investigations carried out in this study include the rheological properties of PLA/ZnO nanoparticles solutions used in the electrospinning of nanofibrous mats and the morphological evaluation of the mats. A detailed rheological analysis of the solutions used for electrospinning was carried out to understand the achieved morphology and structure of nanofibers (NFs). The effect of ZnO nanoparticles (ZnO-NPs) was investigated for various PLA solutions and solvents. The polymer solutions were prepared at various loading levels of ZnO: 0.4, 0.8, 1, 3 and 5 wt% relative to the polymer. Two solvent systems were used: 2,2,2-trifluoroethanol (TFE) and a mixture of dichloromethane/trifluoroethanol (DCM/TFE) (50:50 v/v). PLA with a low loading level of ZnO-NPs showed higher viscosity than neat PLA solutions. They also showed a maximum value of viscosity at 3 wt% content. Solutions containing more than 3 wt% ZnO exhibited a notable decrease in viscosity, which was attributed to PLA degradation. Other nanoparticles (NPs) such as SiO{sub 2} and TiO{sub 2} showed no decrease in the solution viscosity for all concentrations. The morphological characterization of the electrospun nanofibers was performed using scanning electron microscopy (SEM). The SEM images showed a network of smooth, randomly oriented, PLA nanofibers (PLA-NFs) and ZnO agglomeration was observed on the surface of the NFs. In the case of the PLA mats produced from PLA/TFE/ZnO suspensions with decreased viscosity, the SEM results confirmed the generation of beaded-fibers.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2020

Homogeneous titanium hydroxide yields hydroxyl decorated nanofiber separator with improved electrolyte uptake and device capacitance

Good wettability of separators in batteries and capacitors is crucial for performance. Titanium hydroxide (Ti(OH) x ) has been shown to greatly improve the wettability of polyvinylidene fluoride (PVDF) nanofibers (NFs). Here, PVDF/Ti(OH) x NFs were evaluated for their potential use as separators. Results show that PVDF NFs incorporated with Ti(OH) x have improved electrolyte uptake (EU) between 550 and 1200 EU% compared to untreated PVDF with less than 100 EU%. Significant improvements in capacitance are seen from capacitors utilizing PVDF/Ti(OH) x NF separators with the best performing PVDF/Ti(OH) x NF at 15 wt% Ti(OH)x with 446.8 mF/cm 2 compared to untreated PVDF NF separator with 262.7 mF/cm 2 .

36 MATERIALS SCIENCE↗
DOE OSTI2019

Quantifying Polymer Chain Orientation in Strong and Tough Nanofibers with Low Crystallinity: Toward Next Generation Nanostructured Superfibers

Advanced fibers revolutionized structural materials in the second half of the 20th century. However, all high-strength fibers developed to date are brittle. Recently, pioneering simultaneous ultrahigh strength and toughness were discovered in fine (<250 nm) individual electrospun polymer nanofibers (NFs). This highly desirable combination of properties was attributed to high macromolecular chain alignment coupled with low crystallinity. Quantitative analysis of the degree of preferred chain orientation will be crucial for control of NF mechanical properties. However, quantification of supramolecular nanoarchitecture in NFs with low crystallinity in the ultrafine diameter range is highly challenging. Here, we discuss the applicability of traditional as well as emerging methods for quantification of polymer chain orientation in nanoscale one-dimensional samples. Advantages and limitations of different techniques are critically evaluated on experimental examples. It is shown that straightforward application of some of the techniques to sub wavelength-diameter NFs can lead to severe quantitative and even qualitative artifacts. Sources of such size-related artifacts, stemming from instrumental, materials, and geometric phenomena at the nanoscale, are analyzed on the example of polarized Raman method but are relevant to other spectroscopic techniques. A proposed modified, artifact-free method is demonstrated. Outstanding issues and their proposed solutions are discussed. The results provide guidance for accurate nanofiber characterization to improve fundamental understanding and accelerate development of nanofibers and related nanostructured materials produced by electrospinning or other methods. Overall, we expect that the discussion in this review will also be useful to studies of many biological systems that exhibit nanofilamentary architectures and combinations of high strength and toughness.

36 MATERIALS SCIENCE↗
DOE OSTI2015

Modeling the Interaction Between Hydraulic and Natural Fractures Using Dual-Lattice Discrete Element Method

The interaction between hydraulic fractures (HF) and natural fractures (NF) will lead to complex fracture networks due to the branching and merging of natural and hydraulic fractures in unconventional reservoirs. In this paper, a newly developed hydraulic fracturing simulator based on discrete element method is used to predict the generation of complex fracture network in the presence of pre-existing natural fractures. By coupling geomechanics and reservoir flow within a dual lattice system, this simulator can effectively capture the poro-elastic effects and fluid leakoff into the formation. When HFs are intercepting single or multiple NFs, complex mechanisms such as direct crossing, arresting, dilating and branching can be simulated. Based on the model, the effects of injected fluid rate and viscosity, the orientation and permeability of NFs and stress anisotropy on the HF-NF interaction process are investigated. Combined impacts from multiple parameters are also examined in the paper. The numerical results show that large values of stress anisotropy, intercepting angle, injection rate and viscosity will impede the opening of NFs.

02 PETROLEUM↗
DOE OSTI2015

Circumvention of safety related equipment at nuclear fuel services, Inc. - 14570

On June 17, 2014, at Nuclear Fuel Services, Inc. (NFS), an employee was observed improperly operating two (2) spring return (i.e., spring closed) valves identified as Safety Related Equipment (SRE). These valves were also identified as Items Relied on for Safety (IROFS). The valves were important for both Nuclear Criticality Safety (NCS) and Chemical Safety purposes. The valves were observed to be 'propped' in the open position, thereby circumventing the intended safety function of the valves. The event was reported to the NRC Operations Center on June 18, 2014 (Event no. 50208); and, NFS' investigation concluded that the cause (of the event) was due to a willful act by a Nuclear Process Operator. In addition, when reviewing the event for NRC reportability, there was an organizational focus on NCS accident sequences with limited consideration of other aspects of the Integrated Safety Analysis (ISA). In other words, when determining reportability, the performance requirements for NCS accident sequences were reviewed and determined to be satisfied; however, the chemical safety accident sequences had not been considered during this review. The initial event and the reportability issues were entered into NFS' Corrective Action Program (CAP) and investigated. The investigation also included human performance and safety culture implications. This paper summarizes the circumstances surrounding the event and discusses the lessons learned as a result of the event investigation and review. (authors)

42 ENGINEERING↗
DOE OSTI2026

Unbinned extraction of $γ$ from $B\to DK$ with normalizing flows

We introduce an unbinned method for extracting the CKM angle $γ$ from the decay chain $B^\pm \to (D \to K_S π^+ π^-) K^\pm$ using normalizing flows (NFs). The NFs, trained on $D$ decay data, learn a faithful continuous representation of the amplitude and strong phase variation over the $D\to K_Sπ^+π^-$ Dalitz plot whose fidelity improves with increased data sample sizes. With this input, the $B$ decay data can be used to extract the parameters $r_B$, $δ_B$, and $γ$. We test the method on Monte Carlo generated data, where it successfully recovers the injected value of $γ$ within uncertainties. The present implementation propagates statistical uncertainties from finite training data via an ensemble of independently trained flows, and does not attempt to capture the effects of systematic experimental errors. We explore two versions of the method that differ in how the trigonometric constraint on phase variation is encoded, and comment on the possible extension to Bayesian NFs, which would provide direct uncertainty estimates on the learned densities without requiring ensemble training.

Grossman, Yuval [Cornell U., LEPP]↗
DOE OSTI2022

Monolayer Plasmonic Nanoframes as Large‐Area, Broadband Metasurface Absorbers

Abstract Broadband absorbers are useful ultraviolet protection, energy harvesting, sensing, and thermal imaging. The thinner these structures are, the more device‐relevant they become. However, it is difficult to synthesize ultrathin absorbers in a scalable and straightforward manner. A general and straightforward synthetic strategy for preparing ultrathin, broadband metasurface absorbers that do not rely on cumbersome lithographic steps is reported. These materials are prepared through the surface‐assembly of plasmonic octahedral nanoframes (NFs) into large‐area ordered monolayers via drop‐casting with subsequent air‐drying at room temperature. This strategy is used to produce three types of ultrathin broadband absorbers with thicknesses of ≈200 nm and different lattice symmetries (loose hexagonal, twisted hexagonal, dense hexagonal), all of which exhibit efficient light absorption (≈90%) across wavelengths ranging from 400–800 nm. Their broadband absorption is attributed to the hollow morphologies of the NFs, the incorporation of a high‐loss material (i.e., Pt), and the strong field enhancement resulting from surface assembly. The broadband absorption is found to be polarization‐independent and maintained for a wide range of incidence angles (±45°). The ability to design and fabricate broadband metasurface absorbers using this high‐throughput surface‐based assembly strategy is a significant step toward the large‐scale, rapid manufacturing of nanophotonic structures and devices.

36 MATERIALS SCIENCE↗
DOE OSTI2010

Low-spin Fe[superscript 2+] in silicate perovskite and a possible layer at the base of the lower mantle

We investigated the spin state of iron in Mg{sub 0.82}Fe{sub 0.18}SiO{sub 3} silicate perovskite using Moessbauer spectroscopy and nuclear forward scattering (NFS) at pressures up to 130 GPa and temperatures up to 1000 K. Majorite starting material was loaded into diamond anvil cells in three separate experiments, and transformed to silicate perovskite through laser heating. We found, in agreement with previous work, the predominance of a component with high isomer shift ({approx}1 mm/s relative to {alpha}-Fe) and high-quadrupole splitting (QS) (>4 mm/s) in Moessbauer and NFS spectra up to 115 GPa at room temperature, and in accordance with previous work this component was assigned to intermediate-spin Fe{sup 2+}. At higher pressures, the intensity of the high QS component in the silicate perovskite spectrum decreased, while the intensity of a new component with low isomer shift ({approx}0 mm/s relative to {alpha}-Fe) and low quadrupole splitting (<0.5 mm/s) increased. This new component was assigned to low-spin Fe{sup 2+}, and its intensity increased with both increasing pressure and increasing temperature: at 120 GPa and 1000 K all Fe{sup 2+} was in the low-spin state. X-ray diffraction data showed well crystallized perovskite in all runs, and although the stable phase above 110 GPa is expected to be post-perovskite, sluggish transition kinetics likely preserved the perovskite phase in a metastable state. Our results combined with data in the literature and thermodynamic and topological considerations suggest that there may be a region where silicate perovskite containing low-spin Fe{sup 2+} is stable, which coincides with predicted pressure-temperature conditions near the D{double_prime} layer.

36 MATERIALS SCIENCE↗
DOE OSTI2017

MiR-124 down-regulation is critical for cancer associated fibroblasts-enhanced tumor growth of oral carcinoma

Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture. Furthermore, we identified Chemokine (C-C motif) ligand 2 (CCL2) and Interleukin 8 (IL-8) as two direct targets of miR-124. Over-expression of miR-124 in CAFs-OCCs co-culture abrogated CAFs-promoted OCCs cell growth and migration, and this inhibitory effect can be rescued by addition of CCL2 and IL-8. Finally, we showed that restoration of miR-124 expression by lentiviral infection or formulated miR-124 injection inhibited oral tumor growth in vivo suggesting miR-124 rescue could be a potential rationale for therapeutic applications in oral cancer in the future. - Highlights: • miR-124 was downregulated in oral cancer cells and cancer associated fibroblasts. • Hypermethylation in the promoter region was accounted for miR-124 downregulation. • CCL2 and IL-8 are two direct targets of miR-124. • miR-124 rescue could be a potential rationale for oral cancer therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Interaction between oral squamous cell carcinoma cells and fibroblasts through TGF-β1 mediated by podoplanin

Highlights: • Paracrine TGF-β1 from PDPN-positive OSCC cells activates NFs. • PDPN-positive OSCC cells promote fibroblast invasion in direct co-culture. • The fibroblast invasion is promoted through MMP-2, MMP-14, and ITGA5 signaling. • MMP-2 and MMP-14 upregulation by TGF-β1 from CAFs and cancer cells promote OSCC cell invasion. Podoplanin is upregulated in the invasive front of oral squamous cell carcinoma (OSCC). Carcinoma-associated fibroblasts (CAFs) may mediate podoplanin expression. However, the role of podoplanin in OSCC cell and fibroblast interaction remains elusive. In the present study, we found that positive podoplanin expression in OSCC cells correlated with smooth muscle actin (α-SMA) expression in CAFs. Using CAFs and normal mucosal fibroblasts (NFs), we established indirect and direct co-culture systems mimicking the structure of OSCC. Podoplanin-overexpressing OSCC cells promoted NF activation; in direct co-culture, but not in indirect co-culture, podoplanin-overexpressing OSCC cells increased fibroblast invasion via matrix metalloproteinase 2 (MMP-2), MMP-14, and αv/β6 integrin receptor (ITGA5/ITGB6) signaling. CAFs also induced podoplanin expression through the transforming growth factor-β1 (TGF-β1)/Smad pathway. TGF-β1 increased the podoplanin-dependent activation of epidermal growth factor receptor (EGFR), AKT, and extracellular signal–regulated kinase (ERK) signaling. Additionally, CAFs promoted OSCC cell invasion by upregulating MMP-2 and MMP-14 expression in both indirect and direct co-culture. Taken together, our findings indicate that podoplanin regulates the interaction between OSCC cells and CAFs via the mutual paracrine effects of TGF-β1.

60 APPLIED LIFE SCIENCES↗