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) glycoprotein, the expression of which may modulate the invasive and metastatic abilities of cancer cells. LMM3 is a cell line derived from the highly metastatic mouse mammary adenocarcinoma MM3 and is unable to express FN both at protein and mRNA levels. To study the role of FN in the metastatic process, LMM3 cells were stably transfected with 2 variants (wt and RGD-minus) of a full length human FN cDNA. All analyzed clones secreted recombinant FN and although none assembled FN in the ECM they showed an in vitro reduced migratory ability and an increased adhesive capacity. FN-producing cells were assayed for experimental and spontaneous metastasis. All clones tested showed a significant reduction in the number of experimental lung metastasis when compared with a control clone. Similar trends were observed for spontaneous metastatic ability. Our results indicate that the expression of FN that lacks the well-recognized RGD cell-binding site and that does not form ECM fibrils, is 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.