Type-1 transforming growth factor-beta differentially modulates tumoricidal activity of murine peritoneal macrophages against metastatic variants of the B16 murine melanoma.
Transforming growth factor-beta 1 (TGF-beta 1) renders mouse peritoneal macrophages tumoricidal against metastatic variants of the B16 mouse melanoma in vitro. Both direct cytotoxicity and indirect cytotoxicity were observed. A subthreshold concentration (10 U/ml) of recombinant murine interferon-gamma (rMuIFN-gamma) enhanced the direct tumoricidal activity of TGF-beta 1-activated macrophages from 29% to 88% but did not change their indirect tumoricidal profile. Data obtained from macrophages preincubated with either TGF-beta 1 or rMuIFN-gamma showed that TGF-b1 can initiate tumoricidal activity better than rMuIFN-gamma. These effects were plasma-membrane mediated because targeting macrophages with liposomal TGF-beta 1 was ineffective. The order of tumoricidal susceptibility of the B16 melanoma lines to activated macrophages was B16F1 > B16F10 > B16BL6, in inverse order of metastatic potential.
Fan
Dominic
D
Department of Cancer Biology-173, University of Texas, M. D. Anderson Cancer Center, 1515 Holcomble Boulevard, Houston, Texas 77030, USA. dfan@mdanderson.org
Liaw
Amy
A
Denkins
Yvonne M
YM
Collins
James H
JH
Van Arsdall
Melissa
M
Chang
Jolie Lien
JL
Chakrabarty
Subhas
S
Nguyen
Dieuthu
D
Kruzel
Ewa
E
Fidler
Isaiah J
IJ
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D008081:Liposomes; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1