CHEMOTACTIC ACTIVITY PRESENT IN LIVER EXTRACELLULAR-MATRIX

A selective pattern of metastasis, not accountable by a simple mechanical trapping mechanism, is exhibited by many primary tumors and appears to be controlled by properties of both the tumor cell and the host organ. This organotropism may be regulated, in part, by the migration of an invading tumor cell toward chemotactic factors present in the extracellular matrix which may be released as a result of proteolytic digestion. To test this hypothesis we have examined 4M guanidine extracts of liver extracellular matrix, prepared by high salt extraction, for organ-specific chemotactic activity. The murine cell lines B16-L4b and M5076, which preferentially metastasize to the liver in an experimental metastasis model, demonstrated preferential motility toward the liver matrix extract while the lung-colonizing lines B16, B16-F10 and B16-BL6 did not. The liver specific chemotactic activity eluted as four fractions of M(r) >> 250 000, M(r) approximately 245 000, M(r) approximately 120 000 and M(r) approximately 30 000 by gel filtration chromatography.