PROLIFERATION OF LAMA-84 AND LAMA-87 CELL-LINES IS MODULATED BY AUTOCRINE LOOPS INVOLVING M-CSF AND TGF-BETA

The erythromegakaryocytic cell line (LAMA-84) and the erythroeosinophi lic cell line (LAMA-87) were used to study receptor expression and rec eptor-mediated response to monocyte/macrophage colony-stimulating fact or (M-CSF) and transforming growth factor beta (TGF-beta), two modulat ors of cell proliferation. As demonstrated by Northern blot analysis a nd reverse transcriptase polymerase chain reaction (RT-PCR), c-fms and M-CSF mRNA were expressed in both cell lines. M-CSF was detected in t he supernatant of both cell lines and addition of a neutralizing anti- M-CSF antibody inhibited cell growth. The two LAMA cell Lines were fou nd to express TGF-beta 1, -beta 2, and -beta 3 mRNAs and to secrete TG F-beta mostly in latent form. Addition of anti-TGF-beta antibodies to the culture medium increased their proliferation, whereas TGF-beta 1 i nhibited cell proliferation by downregulating the c-myc mRNA. These re sults show that the proliferation of both LAMA cell lines is positivel y and negatively regulated by autocrine mechanisms, implying the prese nce of M-CSF and TGF-beta, respectively. They suggest that similar aut ocrine loops could be involved in the growth regulation of leukemic ce lls in vivo.