EVIDENCE FOR PARACRINE REGULATION OF EXPERIMENTAL METASTASIS IN 13762NF RAT MAMMARY ADENOCARCINOMA CELL CLONES

The ability of tumor cell lines to form experimental pulmonary metasta ses is determined in part by characteristics which are stable over man y cell generations; in part by characteristics that are acquired by ad aptation or phenotypic instability; but also in part by characteristic s which may change over less than one cell generation. This study was designed to examine the hypothesis that tumor cells secrete and respon d to paracrine factors which can reversibly modulate metastasis. The n umber of experimental lung metastases increased for 13762NF rat mammar y adenocarcinoma cell clones MTF7 and MTLn3 as they approach 100% conf luence, This observation corresponded to increased attachment to bovin e brain capillary and bovine corneal endothelial monolayers and to abi lity of tumor cells to invade reconstituted basement membrane barriers in the Membrane Invasion Culture System (MICS), but did not correspon d to cell cycle distribution susceptibility to NK ol PMN cell killing or average cell size/Coulter volume. While changing confluence did not qualitatively alter metastatic potential, modification of metastasis in a quantitative manner suggested that some properties pertinent to m etastasis are transient and manipulatable. Tumor cell-conditioned medi um (CM) collected from donor cells grown to defined levels of confluen ce when placed onto recipient cells reversibly raised or lowered metas tatic potential depending upon the medium source and confluence of the recipient cells. CM from 20% confluent donor cultures reduced recipie nt cell metastatic potential. In contrast CM from 100% confluent cultu res increased metastatic potential of subconfluent cells. Replacement with fresh unconditioned medium or leaving the medium unchanged did no t alter experimental metastasis. These data suggest that metastasis in volves steps which may be influenced by paracrine factors elaborated b y tumor cells.