Neutralizing antibodies against transforming growth factor beta potentiate the proliferation of Ki-1 positive lymphoma cells. Further evidence for negative autocrine regulation by transforming growth factor beta.
Activated lymphocytes and malignant lymphoma cells derived from them (Ki-1 positive lymphoma cells) share similar mechanisms of proliferation. To further examine the inhibitory role of endogenous transforming growth factor beta (TGF beta) in Ki-1 positive lymphoma cells, the authors studied anti-TGF beta antibodies and measured their effect on proliferation. A monoclonal antibody (T1A5) prepared against a unique antigenic epitope of high molecular weight Hodgkin's TGF beta and a polyclonal rabbit antibody prepared against highly purified 25,000 D porcine platelet TGF beta 1 were used. Both antibodies are shown here to inhibit the biological activity of Hodgkin's TGF beta and to crossreact with their respective antigens in immunoblotting. DNA synthesis by Ki-1 lymphoma cells was increased 138-fold by anti-TGF beta 1 antibody and 262-fold by anti-Hodgkin's TGF beta. Exogenous TGF beta 1 suppression was completely reversed by anti-TGF beta 1 antibody and IL-2-induced proliferation was markedly potentiated (41 fold). L-428 Reed-Sternberg cells secrete physiologically active TGF beta but have fewer than 500 TGF beta receptor sites per cell; no significant proliferative response was measured for either anti-TGF beta 1 or anti-Hodgkin's TGF beta. These results show the suppressive effect of exogenous TGF beta 1 on indolent Ki-1 lymphoma cells and suggest that the endogenous secretion of high molecular weight physiologically active TGF beta is important in maintaining the indolent nature of this low-grade Ki-1 positive lymphoma.
Newcom
S R
SR
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Tagra
K K
KK
Kadin
M E
ME
D000906:Antibodies / Q000276:immunology / Q000502:physiology*; D015703:Antigens, CD / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D002455:Cell Division / Q000502:physiology; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D017730:Ki-1 Antigen; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009500:Neutralization Tests; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D007376:Interleukin-2; D017730:Ki-1 Antigen; D016212:Transforming Growth Factor beta