Functions Of Extracellular Matrix Protein TGFBI In Colorectal Cancer Liver Metastasis

The majority of colorectal cancer patients die from recurrence and distant metastasis.Liver metastasis is the leading cause of death in patients with colorectal cancer.Transforming growth factor-beta induced protein(TGFBI)is an extracellular matrix protein that has been reported to be associated with tumorigenesis and the development of tumors.At present,the functions of TGFBI in colorectal cancer liver metastasis is unclear.In this study,we find that TGFBI is highly expressed in AOM/DSS-induced colitis-associated colorectal cancer(CAC)and spontaneous intestinal tumor of ApcMin/+ mice.Moreover,TGFBI is up-regulated in mice colorectal cancer liver metastasis formed by injecting colorectal cancer cells into the spleen.TGFBI is mainly distributed in the interstitial area of liver metastasis and has a good co-localization phenomenon with hepatic stellate cells.We further use the TGFB1 knockout mice to study the role of TGFBI in colorectal cancer liver metastasis.We find that compared to wild-type mice,TGFBI knockout mice with colorectal cancer liver metastasis form less metastatic lesions;knockout of TGFBI significantly inhibits the formation of liver fibrosis and inflammation microenvironment in mice colorectal cancer liver metastasis.In vitro,recombinant TGFBI promotes the migration and invasion of colorectal cancer cells.In addition,we find that TGFBI is highly expressed in the clinical samples of patient with the primary colorectal cancer and liver metastasis.These results suggest that TGFBI promotes the tumorigenesis and development of colorectal cancer liver metastasis,and plays important roles in the liver fibrosis microenvironment and inflammation microenvironment of the progress.This study will help us to further clarify the functions of TGFBI in colorectal cancer liver metastasis and how TGFBI regulates liver tissue microenvironment to promote the development of colorectal cancer liver metastasis.