EXPRESSION OF RGD MINUS FIBRONECTIN THAT DOES NOT FORM EXTRACELLULAR-MATRIX FIBRILS IS SUFFICIENT TO DECREASE TUMOR-METASTASIS

Fibronectin (FN) is a plasma and extracellular matrix (ECM) glycoprote in, the expression of which may modulate the invasive and metastatic a bilities of cancer cells. LMM3 is a cell line derived from the highly metastatic mouse mammary adenocarcinoma MM3 and is unable to express F N both at protein and mRNA levels, To study the role of FN in the meta static process, LMM3 cells were stably transfected with 2 variants (wt and RGD-minus) of a full length human FN cDNA, All analyzed clones se creted recombinant FN and although none assembled FN in the ECM they s howed an in vitro reduced migratory ability and an increased adhesive capacity, FN producing cells were assayed for experimental and spontan eous metastasis. All clones tested showed a significant reduction in t he number of experimental lung metastasis when compared with a control clone. Similar trends were observed for spontaneous metastatic abilit y. Our results indicate that the expression of FN that lacks the well- recognized RGD cell-binding site and that does not form ECM fibrils, i s sufficient to decrease the metastatic potential of cancer cells. Our results also suggest that an RGD-independent mechanism may be acting in the prevention of metastasis. (C) 1998 Wiley-Liss, Inc.