The SFL activity secreted by metastatic carcinoma cells is related to laminin 5 and mediates cell scattering in an integrin-independent manner.
We have previously reported that an in vivo-selected metastatic variant of NBT-II rat carcinoma cells, M-NBT-II, produces and secretes a factor with cell-scattering activity, SFL, that is potentially involved in tumor progression. This biological activity was purified and characterized as a laminin 5 (LN5) -related protein. This SFL/LN5 protein consists of the (alpha)3, (beta)3 and (gamma)2 chains of expected sizes. Laminin 5 is a multifunctional secreted glycoprotein thought to be involved in cell adhesion and migration, mainly via its interaction with (alpha)3(beta)1 and (alpha)6(beta)4 integrins. SFL/LN5, and purified human laminin 5, induced the scattering and motility of MDCK cells and the formation of actin stress fibers and focal contacts in A549 cells. These events were dependent on activation of the small GTP-binding protein Rho. (Alpha)v colocalized with vinculin in the focal contacts of activated cells whereas (alpha)3 and (alpha)6 integrins did not. Blocking antibodies directed against (alpha)3 and (alpha)6 integrins or the laminin 5 integrin-binding site did not abolish SFL/LN5 biological activity, which, in contrast, was completely inhibited by heparin. Thus, SFL/LN5 activity in epithelial cell scattering and cytoskeletal reorganization is probably independent of integrin receptors.
Grassi
M
M
Laboratoire de Morphogénèse cellulaire et Progression tumorale, CNRS/Institut Curie, UMR 144, 75248 Paris Cedex 05, France.
Moens
G
G
Rousselle
P
P
Thiéry
J P
JP
Jouanneau
J
J
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008207:Lymphatic Metastasis; D009362:Neoplasm Metastasis; D051381:Rats; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D019204:GTP-Binding Proteins; D016023:Integrins; D000097794:Kalinin