Effects of a fibroblast-derived inhibitor on the growth of normal marrow and leukemic clonogenic cells

Abstract

Blood cells develop in the bone marrow, controlled by a network of regulatory factors, some of which originate in the stroma. Previously, we found that most fibroblastoid (FB) cells growing in primary cultures of rat marrow bear surface antigens different from those found on FB of certain other tissues. As determined by two monoclonal antibodies (“ST3” and “ST4”), the “marrow type” is ST3 +/ST4 − and releases predominantly a colony-stimulating activity (CSA) into its culture media (CM), whereas the “peripheral type” (e.g. lung) is predominantly ST3 −/ST4 + and produces inhibitory activity in excess of CSA. The studies described here show that this inhibitor also is active on rat leukemic myeloblasts (the BNML cell line), but not on eight other cell lines derived from rat tumors of various origins or on the human-derived leukemic cell lines tested. It was produced without exogenous stimulation, was labile to heat and acid, was not neutralized by antisera to transforming growth factor-beta, beta-interferon, or ferritin, and had an apparent mol wt in the range of 100–120 kD (peak of activity by gel filtration). From the results obtained at this time, we are not able to ascribe this fibroblast-derived activity to any known inhibitor molecule.