Peptide fragments of laminin and fibronectin promote migration (haptotaxis and chemotaxis) of metastatic cells.

The migration of tumour cells through basement membranes and extracellular matrices is an integral component of tumour invasion and metastasis. Laminin (LMN) and fibronectin (FN) at 1-100 micrograms/ml promote the directed migration of metastatic murine melanoma cells 40-70-fold greater than controls in modified Boyden chambers. Antibodies abrogated the migration of cells in response to the respective protein. Preincubation of melanoma cells with plasma FN had no effect on subsequent migration to LMN or FN. The migration of these cells was largely related to substratum-attached molecules and increasing adhesion gradients of cells; this has been termed haptotaxis. Peptide fragments of both FN and LMN were isolated by affinity chromatography with monoclonal antibodies, heparin or other constituents. FN has two unique domains, 80-125 K and 66 K, which promote the adhesion of tumour cells, whereas only one appeared to be responsible for promoting migration. Peptides of LMN, isolated with heparin and monoclonal antibody, define a cell migration-promoting activity within the 200 K chains of LMN. Serum spreading factor and epinectin, the latter an adhesion molecule derived from squamous epithelial tumour cells, are also capable of promoting the migration of malignant cells. Thus, directed migration of metastatic tumour cells may be promoted with peptide fragments of adhesion molecules and blocked with the respective antibody.