HGF/MET Axis Induces Tumor Secretion of Tenascin-C and Promotes Stromal Rewiring in Pancreatic Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Co-Culture Models
2.3. Western Blot Analysis
2.4. RNA Analysis and Real-Time PCR
2.5. Immunofluorescence
2.6. In Vivo Experiments
2.7. Generation of TNC-shRNA HPAF-II Cells
2.8. Statistical Analysis
3. Results
3.1. Inhibition of the HGF/MET Axis Reduces Activation of Pancreatic Stellate Cells
3.2. Transcriptional Gene Expression Profiling of HPAF-II PDAC Cells in Response to HGF/MET Pathway Modulation
3.3. TNC: A Candidate Mediator in HGF/MET-Dependent Tumor-Stroma Cross-Talk
3.4. Validation of TNC Modulation Following Inhibition of the HGF/MET Axis in Pancreatic Cancer Cells In Vitro
3.5. Validation of TNC Modulation and Reduction of Stroma Activation Following Inhibition of the HGF/MET Axis in PDAC Tumors In Vivo
3.6. HGF/MET-Dependent Tumor-Stroma Cross-Talk Is Mediated by TNC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
α-SMA | Alpha-smooth muscle actin |
FAP | Fibroblast-activating protein |
HGF | Hepatocyte growth factor |
IPA | Ingenuity pathway analysis |
MFI | Mean fluorescence intensity |
PDAC | Pancreatic ductal adenocarcinoma |
PSCs | Pancreatic stellate cells |
qRT-PCR | Quantitative real-time polymerase chain reaction |
RNAseq | RNA-sequencing-based gene expression analysis |
SCID | Severe combined immunodeficiency |
SD | Standard deviation |
SEM | Standard error of the mean |
TNC | Tenascin C |
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Modica, C.; Olivero, M.; Zuppini, F.; Milan, M.; Basilico, C.; Vigna, E. HGF/MET Axis Induces Tumor Secretion of Tenascin-C and Promotes Stromal Rewiring in Pancreatic Cancer. Cancers 2021, 13, 3519. https://doi.org/10.3390/cancers13143519
Modica C, Olivero M, Zuppini F, Milan M, Basilico C, Vigna E. HGF/MET Axis Induces Tumor Secretion of Tenascin-C and Promotes Stromal Rewiring in Pancreatic Cancer. Cancers. 2021; 13(14):3519. https://doi.org/10.3390/cancers13143519
Chicago/Turabian StyleModica, Chiara, Martina Olivero, Francesca Zuppini, Melissa Milan, Cristina Basilico, and Elisa Vigna. 2021. "HGF/MET Axis Induces Tumor Secretion of Tenascin-C and Promotes Stromal Rewiring in Pancreatic Cancer" Cancers 13, no. 14: 3519. https://doi.org/10.3390/cancers13143519