Résumé
Abstract only Transforming growth factor‐beta‐induced protein ig‐h3 (TGFBI) is an important actor of the extracellular matrix. While elevated expression of TGFBI has been reported in human cancer, its role still remains controversial. We show here for the first time that TGFBI is a relevant factor for VEGF expression in cancer cells. As evidenced by immunohistochemistry, high level of TGFBI is a constitutive feature of human colorectal cancer liver metastases (CRC‐LM). To assess its function in cancer, we silenced TGFBI in human CRC cells. The suppression of the TGFBI protein decreased cancer cells migration and proliferation. In vivo, TGFBI silencing resulted in a 50% decrease in the volume of CRC tumors grown on a chicken chorioallantoic membrane (CAM). Low vascularization of these tumors suggested an additional anti‐angiogenic effect. Indeed, we found that TGFBI knockdown in SW1222 cells altered the secretion of VEGFA and led to an impairment of the subsequent signaling pathway. This observation was in line with previous data showing that TGFβ was able to induce TGFBI in cancer cells, forging a direct functional link to angiogenesis. Finally, to test if TGFBI could be a relevant target for antibody‐drug delivery, we injected a fluorescently labeled anti‐TGFBI antibody in mice bearing liver metastases. The in vivo data demonstrated that TGFBI is an accessible tumor target. Taken together, our study shows that TGFBI is essential for the development of CRC‐LM and therefore represents a promising target for novel therapeutic approaches. Grant Funding Source : Supported by FNRS and the University of Liege