Motility and adhesive properties of high- and low-metastatic murine neoplastic cells.

Randomly chosen clones of the murine K-1735 melanoma tumor were used by Raz and Geiger to address the question of whether variations in actin organization in these cells may be related to their lung colonization capability in syngeneic hosts (Cancer Res., 42: 5183-5190, 1982). In 14 of 15 clones tested, we found that the degree of actin organization was inversely correlated to their metastatic capability. We have further shown that remarkable variations exist in the adhesive properties and locomotor activity of four K-1735 melanoma cell variants that exhibit distinct metastatic properties. The low-metastatic cell variants displayed large focal adhesion plaques, tightly packed actin bundles, elaborate extracellular networks of fibronectin, and restricted motility. In contrast, the high-metastatic variants were poorly attached with only few distinct actin bundles, were unable to reorganize extracellular fibronectin into cables, and exhibited high motile activity. Electron microscopic examination of local s.c. tumors of the high- and low-metastatic lines indicated that the former formed loose tumor masses with very few intercellular connections, while the low-metastatic line developed into a considerably more compact tumor with numerous intercellular contacts, in line with the in vitro findings. It is proposed that the differences in cellular properties manifested by these cell lines may be related to their metastatic properties. Specifically, the highly metastatic cells of this tumor system may easily detach from the primary tumor mass, form weak and transient connections with surrounding connective tissue, and actively migrate through it. Furthermore, these results point to the close interrelationships between different mechanochemical features in cells, including specific cell adhesiveness, cytoskeletal organization, locomotion, and rearrangement of extracellular fibronectin. The possible nature of these interrelationships is discussed.