Transforming growth factor‐beta‐induced protein ig‐h3 is essential for the formation of human colorectal carcinoma liver metastasis in vivo

Abstract

Transforming growth factor‐beta‐induced protein ig‐h3 (TGFBI) is extracellular matrix component important for cell‐collagen interaction. We and others have reported elevated expression of TGFBI in several human cancers, where its role remains controversial. Current study reports for the first time on the function of TGFBI in colorectal carcinoma liver metastasis (CRC‐LM), a frequently encountered malignancy with no satisfactory treatment to date.We show that TGFBI is highly expressed in human CRC‐LM and in LM originating from breast, lung and pancreatic tumors. From functional perspective, silencing TGFBI in SW1222 human colorectal carcinoma cells lead to a decrease in migration (−70%) and proliferation (−20%). To understand how this effects translate 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 vivo. Finally, we have demonstrated that TGFBI is systemically reachable target for homing fluorescently‐labeled antibodies injected in tumor bearing animals. Collectively the data show that TGFBI is essential for promoting the development of CRC‐LM and therefore a promising target for designing novel therapeutic approaches.This work is supported by FNRS, Belgium and FP7 EU program.