DIFFERENCES IN EXPRESSION OF METALLOPROTEINASES AND PLASMINOGEN ACTIVATORS IN MURINE MELANOCYTES AND B16 MELANOMA VARIANTS - LACK OF ASSOCIATION WITH IN-VITRO INVASION

We investigated in vitro chemotactic responses to fibronectin and lami nin, invasion through reconstituted basement membrane (Matrigel) and s ecretion of matrix metalloproteinases and plasminogen activators by no n-tumorigenic Mel-ab melanocytes; B16 melanoma; and the metastatic sub lines, B16F1, B16F10 and B16BL6. In vitro chemotactic and invasive abi lity were not associated with in vivo metastatic potential. Secretion of various matrix-degrading enzymes was not related to in vitro invasi on. Conditioned media from all Bib melanoma sublines, but not from Mel -ab tells, contained the M(r) 92,000 progelatinase. The activated M(r) 85,000 species was present only in conditioned media from Mel-ab, B16 and B16F1 cells. Mel-ab cells secreted copious amounts of the M(r) 72 ,000 pro-gelatinase, and the M(r) 66,000 active form was also present in conditioned media. Secretion of the M(r) 72,000 pro-gelatinase by B 16 melanoma sublines was markedly lower, and only conditioned media fr om B16 cells contained the activated M(r) 66,000 form. Furthermore, ce ll lysates of Mel-ab cells contained a M(r) 67,000 metalloproteinase w hich was absent in the tumor cells. All cells secreted tissue plasmino gen activator; however, the metastatic B16F1, B16F10 and B16-BL6 cells also secreted urokinase plasminogen activator. Our results indicate t hat matrix metalloproteinase secretion by itself is not associated wit h tumorigenicity or metastatic potential. Secretion of urokinase plasm inogen activator, and not tissue plasminogen activator, reflected the metastatic: characteristics of the B16 melanoma tumor sublines. (C) 19 95 Wiley-Liss, Inc.