title: Role of tumor-derived transforming growth factor-beta1 (TGF-beta1) in site-dependent tumorigenicity of murine ascitic lymphosarcoma.
abstract: An ascitic lymphosarcoma (LS-A) of Swiss mice that regressed spontaneously on subcutaneous (s.c.) transplantation was investigated for the mechanism of its progressive growth and host mortality on intraperitoneal (i.p.) transplantation. In vitro studies indicated significant inhibition of LS-A proliferation seeded at higher cell density (>10(4)/ml). Culture supernatants of LS-A caused bi-modal growth effects, the early supernatants (24 h) caused stimulation and the late (72 h) supernatants inhibited LS-A proliferation. The 72-h supernatants also suppressed T and B cell response to mitogens in a dose-dependent manner. Pan anti-transforming growth factor-beta antibody abrogated the inhibitory effects of supernatants. The supernatants contained both latent as well as bio-active form of transforming growth factor-beta1 (TGF-beta1) as determined by ELISA. Mice bearing i.p. ascites tumor had elevated serum TGF-beta1, hemoglobulinemia, splenic lymphopenia, impaired response of the T cells to mitogen and reduced expression of transferrin receptor (CD71) on the bone marrow cells. However, mice which rejected s.c. transplants, did not show significant changes in these parameters. Our studies indicated profound influence of site of tumor growth on tumor progression and host immune system mediated by tumor-derived TGF-beta1. It is possible that human tumors which secrete TGF-beta1 may exhibit similar patho-physiological effects in the host depending on the anatomical site of the tumor.
authors.affiliation: Radiation Biology & Health Sciences Division, Bioscience Group, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: V S
authors.initials: VS
authors.lastname: Thakur
authors.forename: B
authors.initials: B
authors.lastname: Shankar
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
authors.forename: S
authors.initials: S
authors.lastname: Premachandran
authors.forename: K B
authors.initials: KB
authors.lastname: Sainis
mesh_terms: D000740:Anemia / Q000097:blood / Q000209:etiology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001201:Ascites; D049109:Cell Proliferation; D018450:Disease Progression; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008231:Lymphopenia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D011990:Receptors, Transferrin; D012513:Sarcoma, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D006454:Hemoglobins; D008934:Mitogens; D011990:Receptors, Transferrin; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
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