Down regulation of cell adhesion via rho associated protein kinase (ROCK) pathway promotes tumor cell migration on laminin 511.
Epithelial cells, both normal and precancerous, stably anchor to basement membranes, whereas malignant tumors pass through them to achieve metastasis. Of basement membrane components, laminin 511 (a5, b1, g1; LM 511) has been found to be a major isoform in many adult basement membranes. Several studies have shown that LM 511 promotes not only cell adhesion but also tumor cell migration. Thus, LM 511 can be viewed like two distinct molecules in normal vs. tumor cells; tumor cells seem to be able to alter their response (adhesive vs. migratory) to LM 511. In this study we examined the effects of biologically active molecules on A549 lung adenocarcinoma cell adhesion to LM 511. Of them, phorbol 12 myristate 13 acetate (PMA) induced transition to a rounded cell shape and significantly promoted cell migration on LM 511. The attachment of PMA treated A549 cells to LM 511 was weaker than that of control cells. PMA stimulated signaling pathway reduced the binding of integrin a3b1 to LM 511. Cell migration assays using inhibitors for signal transduction and cytoskeletal organization showed that suppression of cell adhesion via the rho associated protein kinase (ROCK) pathway promoted tumor cell migration on LM 511. Our results suggest that the ROCK pathway is involved in the transition from static to migratory cell behaviors on LM 511.
Experimental cell research