Modulation of cell adhesion and proliferation by cell adhesion regulatory peptides derived from fibronectin and tenascin

Integrin-mediated cell adhesion to extracellular matrix (ECM) is implicated in the regulation of cellular processes, such as growth, differentiation, migration and apoptosis. Integrin α4β1 interacts with VCAM-1 on venule endothelial cell surface as well as CS-1 region of fibronectin (FN) molecule, which plays an important role in leukocyte infiltration, lymphocyte homing, and even tumor metastasis. On the other hand, we have found that FN and tenascin(TN)-C have cryptic functional d sites regulating cell adhesion to ECM. FN- and TN-peptides containing these functional sites termed FMII14 and TNIII negatively and positively positively regulate the integrin-mediated cell adhesion, respectively. Here we examine effects of our adhesion regulatory peptides on cell adhesion and growth. Integurin α4β1-mediated adhesion of B limphoma Ramos cells to FN was suppressed by FNIII14, but stimulated by TNIII. The adhesion stimulatory effect of TNIII was reversed by FNIII14. Then, we examined wheter Ramos cell prolifecation was affected when their adhesion to FN was varied by our peptids. Ramos cell proliferation was significantly suppressed by TNIII, and FNIII14 reversed the effect of TNIII. This growth suppression by TNIII was accompanied by apoptotic death of Ramos cells which was reversed by FNIII14, suggesting that suppression of Ramos cell proliferation by peptide TNIII might be, at least in part, due to apoptosis. Finally, TNIII was shown to be capable of down-regulating the Bcl-2 expression. In conclusion, peptide FNIII14 and TNIII have the high potential to control cell growth/apoptosis as well as cell adhesion to ECM.