DDR2 Expression in Cancer-Associated Fibroblasts Promotes Ovarian Cancer Tumor Invasion and Metastasis through Periostin-ITGB1
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials (or Subjects) and Methods
2.1. Cell Culture
2.2. Primary Cancer-Associated Fibroblast Cell Culture
2.3. Secretome Protein Analysis
2.4. Genetic Knockdown and Overexpression
2.5. Tumor Cell Spreading
2.6. 3D Collagen Invasion
2.7. Mesothelial Cell Clearance
2.8. Attachment Assay
2.9. Transwell Invasion Assay
2.10. Wound Healing Assay
2.11. Statistical Analysis
2.12. Western Blot Analysis
2.13. Co-Immunoprecipitation Assay
2.14. cDNA Preparation and Quantitative Real-Time PCR
2.15. Xenograft Model of Ovarian Cancer
2.16. Immunohistochemistry and Tumor Microarray
2.17. TCGA RNA Co-Expression
3. Results
3.1. CAFs Promotes Ovarian Tumor Spheroid Branching through DDR2
3.2. Fibroblast DDR2 Expression Regulates Periostin (POSTN) Levels
3.3. Regulation of Periostin by DDR2 Promotes the Steps of Tumor Metastasis in Cell-Based Assays
3.4. Regulation of Periostin by DDR2 Increases Tumor Spreading and Proliferation
3.5. Regulation of POSTN by DDR2 Influences PI3K/Akt and Src Pathways
3.6. DDR2 Regulates Integrin β1 (ITGB1) Which Binds Directly to Periostin
3.7. Regulation of Periostin by DDR2 Promotes Tumor Implantation In Vivo
3.8. POSTN Expression Correlates with DDR2 Expression in Patient Tumors
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Akinjiyan, F.A.; Dave, R.M.; Alpert, E.; Longmore, G.D.; Fuh, K.C. DDR2 Expression in Cancer-Associated Fibroblasts Promotes Ovarian Cancer Tumor Invasion and Metastasis through Periostin-ITGB1. Cancers 2022, 14, 3482. https://doi.org/10.3390/cancers14143482
Akinjiyan FA, Dave RM, Alpert E, Longmore GD, Fuh KC. DDR2 Expression in Cancer-Associated Fibroblasts Promotes Ovarian Cancer Tumor Invasion and Metastasis through Periostin-ITGB1. Cancers. 2022; 14(14):3482. https://doi.org/10.3390/cancers14143482
Chicago/Turabian StyleAkinjiyan, Favour A., Ritu M. Dave, Emily Alpert, Gregory D. Longmore, and Katherine C. Fuh. 2022. "DDR2 Expression in Cancer-Associated Fibroblasts Promotes Ovarian Cancer Tumor Invasion and Metastasis through Periostin-ITGB1" Cancers 14, no. 14: 3482. https://doi.org/10.3390/cancers14143482