SFL PRODUCTION BY CARCINOMA-CELLS INDUCES THE AGGRESSIVE PROPERTIES OF NONPRODUCING CELLS IN-VIVO VIA A COMMUNITY EFFECT

A metastatic rat bladder carcinoma cell line, M-NBT-II, produces and s ecretes a dissociating factor called SFL, whereas the tumorigenic pare ntal cell line from which it originated (E-NBT-II) does not. In this w ork, we report that SFL production is correlated with an invasive phen otype in three-dimensional collagen gels or organotypic cocultures. Th is invasiveness may be related to the production of gelatinolytic acti vity. We have also investigated the behavior of SFL-producing cells wi thin an NBT-II solid tumor. Here we report that the presence of 14% of SFL-factor-producing cells are sufficient to increase the tumorigenic ity, and subsequently the metastatic behavior, of the entire cell popu lation, indicating that there is no clonal dominance of the SFL-produc ing cells for tumorigenicity and metastatic spreading, but rather a co mmunity effect. SFL factor may contribute to cell-cell cooperativity b y paracrine or other indirect mechanisms.