Résumé
Introduction : Transforming growth factor-beta-induced protein ig-h3 (TGFBI) is extracellular matrix component known to be important for cell-collagen interaction. We and others have reported elevated expression of TGFBI in sev- eral human cancers, where its role remains controversial. Aim Current study aims at clarifying the function of TGFBI to date.
Methods &Results : CRC-LM and in liver metastases originating from breast, lung and pancreatic tumors. We have next focused on func- tional aspects and have silenced TGFBI expression in SW1222 human colorectal carcinoma cells. The suppression of TGFBI protein led to a marked decrease in cell migration (-70%) and proliferation (-30%) in vitro. To study the effects in vivo we have developed a novel animal model of colorectal carcinoma based on chicken chorioallantoic membrane (CAM) that mimics human CRC-LM. TGFBI silencing resulted in 50% reduction of tumor volume in the CAM tumor model. Notably, the tumors displayed a marked inhibition of vascularization, suggesting an additional anti-angiogenic effect. Indeed, SW1222 cells silenced for TGFBI expression secreted lower levels of VEGFA in vitro. Finally, we have investigated if TGFBI can be used as systemically reachable target for antibody-drug delivery. For this purpose we have The in vivo data demonstrated that TGFBI is an accessible tumor target.
Conclusions : Taken together, the present study shows that TGFBI is essential for promoting the development of CRC- LM and therefore represents a promising target for designing novel therapeutic approaches.