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 erythroeosinophilic cell line (LAMA-87) were used to study receptor expression and receptor-mediated response to monocyte/macrophage colony-stimulating factor (M-CSF) and transforming growth factor beta (TGF-beta), two modulators of cell proliferation. As demonstrated by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR), c-fms and M-CSF mRNA were expressed in both cell lines. M-CSF was detected in the supernatant of both cell lines and addition of a neutralizing anti-M-CSF antibody inhibited cell growth. The two LAMA cell lines were found to express TGF-beta1, -beta2, and -beta3 mRNAs and to secrete TGF-beta mostly in latent form. Addition of anti-TGF-beta antibodies to the culture medium increased their proliferation, whereas TGF-beta1 inhibited cell proliferation by downregulating the c-myc mRNA. These results show that the proliferation of both LAMA cell lines is positively and negatively regulated by autocrine mechanisms, implying the presence of M-CSF and TGF-beta, respectively. They suggest that similar autocrine loops could be involved in the growth regulation of leukemic cells in vivo.
Champelovier
P
P
Laboratoire de Cytologie, Centre Hospitalier Régional et Universitairede Grenoble, France.
Fixe
P
P
Valiron
O
O
Feige
J J
JJ
Praloran
V
V
Seigneurin
D
D
D000818:Animals; D001752:Blast Crisis; D015152:Blotting, Northern; D002455:Cell Division; D017077:Culture Media, Conditioned; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016173:Macrophage Colony-Stimulating Factor; D012194:RNA-Directed DNA Polymerase