TGFBI Inhibits Cell Proliferation And Invasion In Malignant Mesothelioma And Breast Cancer In Vitro And In Vivo

TGFBI (transformaing growth factorβinduced) has been demonstrated to regulate cellular adhesion and migration and implicated as function of extracellular matrix (ECM). More recently, the down-regulation of TGFBI has been found in lung, mammary and prostate cancer. The present study was focused on ascertaining how TGFBI affects cell proliferation and invasion in malignant misothelioma cells (NCI-H28) and breast cancer cells (MDA-MB-231), which both in vitro and in vivo conditions. The pRc/CMV2-TGFBI vectors was transfected into different cell lines and multiple mesothelioma cell clones (T2804, T2806 and T2807) and breast cancer cell clones (T23108, T23109, and T23113), which expressed high levels of TGFBI were established. Results showed that population doubling time of NCI-H28 and MDA-MB-231 cells dramatically increased by 4.38 and 1.16 folds after reintroducting of TGFBI. Consistently, the cells proliferation rate, significantly decreased with the expression of TGFBI. Furthermore, TGFBI expression resulted in a significant inhibition of anchorage-independent growth among cancer cell lines, by reducing growth 48.54% in mesotheloma cells and 90.89% in breast cancer cells, respectively. Flow Cytometry analysis indicated that the distribution of S phase cells among cancer cell lines was remarkably decreased by TGFBI expresion, whereas, G1 phase was significantly increased. The redistribution of cell cycle phase could be attributed by the transient evelation of p21 and p53 which also coupled with increase in cellular senensence. In vitro matrigel invasion assay was adopted to estimate the metastatic characteristic. Surprisingly, TGFBI's re-expression markedly impaired the invasion behaviors of mesothelioma and breast cancers by 45.01% and 37.62%, respectively. This correlated with a reducting of MMP2/9 activity and an increase in cell adhesion to the mixed ECM of rh-TGFBI and Fibronectin with ectopic expression of TGFBI. Parental and TGFBI-expressed breast cancer cells were subcutaneously inoculated into nude mice. TGFBI expression decreased tumorigenicity by 16.99% and delayed the latency of tumor growth. Immunohistochemical staining showed that TGFBI re-expression decreased the percentage of Ki-67 and MECA-32 positive cells in tumor tissues. In summery, the results indicated that TGFBI exhibits a tumor suppressor function by ways of inhibiting cell proliferation and invasion in vitro and in vivo in mesothelioma and breast cancer.