Role of tumor-derived transforming growth factor-beta1 (TGF-beta1) in site-dependent tumorigenicity of murine ascitic lymphosarcoma.
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.
Thakur
V S
VS
Radiation Biology & Health Sciences Division, Bioscience Group, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
Shankar
B
B
Chatterjee
S
S
Premachandran
S
S
Sainis
K B
KB
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
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
Toxicol Appl Pharmacol. 2002 Nov 15;185(1):48-54
12460736
Trends Cell Biol. 2001 Nov;11(11):S44-51
11684442
Eur J Cancer. 1994;30A(14):2125-9
7857713
J Exp Ther Oncol. 2002 Sep-Oct;2(5):286-97
12416032
Cancer. 1999 Feb 1;85(3):554-61
10091729
Int J Oncol. 1993 Mar;2(3):393-8
21573567
Cytokine Growth Factor Rev. 1999 Jun;10(2):99-117
10743502
Cancer Res. 1990 Dec 15;50(24):7775-80
2253220
Cytokine. 2003 Jan 21;21(2):98-104
12670449
Int J Cancer. 1994 Aug 1;58(3):440-5
8050825
Cancer Res. 1994 Jan 15;54(2):575-81
8275496
Indian J Exp Biol. 1997 Jun;35(6):581-8
9357160
J Immunol Methods. 2001 Dec 1;258(1-2):193-8
11684136
Philos Trans R Soc Lond B Biol Sci. 1990 Mar 12;327(1239):145-54
1969655
Int J Cancer. 1992 Aug 19;52(1):98-104
1500231
Int J Cancer. 1967 Sep 15;2(5):421-4
6083257
Biochem J. 2000 Dec 15;352 Pt 3:601-10
11104663
Int Immunol. 2001 Feb;13(2):233-40
11157856
Am J Obstet Gynecol. 1996 Dec;175(6):1489-92
8987930
Proc Natl Acad Sci U S A. 1997 May 27;94(11):5877-81
9159168
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82
8710843
Oncogene. 2002 Feb 28;21(10):1616-24
11896591
Immunol Today. 1997 Oct;18(10):493-7
9357142
Recent Prog Horm Res. 1988;44:157-97
3064207
Cancer Treat Rev. 1996 Nov;22(6):395-423
9134002
J Immunol. 1988 Jun 15;140(12):4217-23
3131428
J Exp Med. 1986 May 1;163(5):1037-50
2871125
Cancer Res. 1984 Nov;44(11):5286-90
6333272
J Immunol. 1989 Nov 15;143(10):3222-9
2809198
Surgery. 1999 Sep;126(3):562-7
10486610
J Postgrad Med. 1992 Jan-Mar;38(1):8-9
1512732
Am J Pathol. 1998 Oct;153(4):1249-56
9777956
Int J Oncol. 1999 Dec;15(6):1155-62
10568822
J Natl Cancer Inst. 1990 Dec 19;82(24):1890-8
2174463
Tumour Biol. 1985;6(1):89-98
4023565
Cancer Immunol Immunother. 1997 Jan;43(6):317-23
9067402