ENHANCEMENT OF J6-1 HUMAN LEUKEMIC-CELL PROLIFERATION BY CELL-CELL CONTACT - ROLE OF AN M-CSF-LIKE MEMBRANE-ASSOCIATED GROWTH-FACTOR MAF-J6-1

Density-dependent cell proliferation and cluster formation are growth phenotypes frequently associated with leukemia cells. The secretion of autocrine growth factor, such as granulocyte-macrophage colony stimul ating factor (GM-CSF) and interleukin 1 (IL-1), has been implicated as one possible mechanism in leukemogenesis. In many cases, however, leu kemia cells do not appear to produce autocrine growth stimulators. J6- 1 is an established human myeloid leukemia cell line that exhibits bot h density-dependent and cluster-forming growth characteristics. The ef fect of direct cell-cell contact on J6-1 cell proliferation was invest igated. We have isolated from J6-1 cells a membrane-bound factor (desi gnated as MAF-J6-1) that promoted the colony formation by both J6-1 ce lls and mouse bone marrow CFU-GM. The growth-promoting activity of MAF -J6-1 can be neutralized by either anti-macrophage-CSF (M-CSF or CSF-1 ) or anti-MAF-J6-1 monoclonal antibodies (MAb), suggesting that MAF-J6 -1 is related to M-CSF. Using an immunoblot analysis with anti-MAF-J6- 1 MAb, the MW of this membrane-associated factor was estimated to be 8 0 kDa. Both antibodies also induced a modest growth inhibition on J6-1 cells in vitro. Similarly, addition of exogenous recombinant human M- CSF augmented the colony formation by J6-1 cells, an effect also neutr alized by both antibodies. Using an in situ hybridization technique, J 6-1 cells were found to express a high level of c-fms proto-oncogene, which encodes the receptor for the M-CSF. Taken together, our results suggest that the membrane-bound MAF-J6-1 promote J6-1 cell proliferati on and cluster formation through a 'juxtacrine' mechanism.