COLLAGEN DEGRADATION BY METASTATIC VARIANTS OF LEWIS LUNG-CARCINOMA - COOPERATION BETWEEN TUMOR-CELLS AND MACROPHAGES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (11) , 5321-5327
Abstract
Interactions between cancer cells and host macrophages might have important regulatory roles in controlling the expression of the metastatic phenotype, particularly by regulating the production of proteases necessary for tissue invasion. To investigate that possibility, mouse macrophages and Lewis lung carcinoma (LLC) cells from 4 clonal subpopulations with low or high metastatic ability were cultured on [14C]collagen (type 1)-coated plates. They did not degrade collagen when they were cultured independently on that substrate, but they were induced to do so when macrophages and cancer cells were cultured together. An increased production of neutral collagenase and other neutral protease activities was observed simultaneously. The degree of stimulation of collagen degradation varied according to the cancer cell subpopulation present in the cocultures. For a given LLC cell subpopulation, similar degrees of stimulation of collagen degradation were achieved with bone marrow-derived or resident peritoneal macrophages, syngeneic (from C57BL/6 mice) or allogeneic; lower stimulations were obtained with thioglycolate-elicited peritoneal macrophages. Macrophage-conditioned culture media could be substituted for living macrophages to stimulate collagen degradation or collagenase secretion by LLC cells, but LLC cell-conditioned media did not stimulate collagen degradation by macrophages. This suggests that, in the cocultures, collagen degradation is achieved mainly by the cancer cells, not by the macrophages, and that it is induced by a soluble factor, a monokine, produced by the macrophages.

This publication has 2 references indexed in Scilit: