Collagen V Has A Role In The Extracellular Matrix Radiation Response

The extracellular matrix (ECM) is a complex meshwork of insoluble fibrillary proteins and signalling factors interacting together to provide architectural and instructional cues to surrounding cells. Alterations in ECM organization or composition and excessive ECM deposition have been observed in diseases such as fibrosis, cardiovascular diseases and cancer. Due to its complexity, ECM involvement in cancer is still poor understood, and its role in radiation response is unknown.

We used mouse models of colorectal and pancreatic cancer to investigate the effects of ionising radiation on tumour microenvironment. Using quantitative proteomics, we identified 104 ECM proteins, which revealed robust ECM signatures. This analysis indicated a significant decrease in Collagen V, a regulatory fibril-forming collagen that forms heterotypic fibrils with Collagen I, in the irradiated samples compared with the non-irradiated whereas Collagen I expression does not change. We confirmed this data with RT-PCR and WB analysis. Using picrorius red stainings we found that collagen deposition was significantly alterated by irradiation. In addition, five collagen architectural parameters (alignment, density, width, length and straightness) were analysed with second harmonic generation imaging, a highly specific technology for detection of collagen fibers.

Our data indicated that there is a significant decrease in collagen width after irradiation in pancreatic cancer model and in the colorectal cancer model. In vitro assays showed that Collagen V gene knock down significantly decrease cell survival (CFA) upon IR and cell migration (3D-spheroids).

Our findings suggests that a decrease in Collagen V lead to ECM alterations and has a role in the radiation response.