TY - JOUR
T1 - Anti-transforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity
T2 - Implications for a possible role of tumor cell/host TGF-β interactions in human breast cancer progression
AU - Arteaga, C. L.
AU - Hurd, S. D.
AU - Winnier, A. R.
AU - Johnson, M. D.
AU - Fendly, B. M.
AU - Forbes, J. T.
PY - 1993/12
Y1 - 1993/12
N2 - TGF-β effects on angiogenesis, stroma formation, and immune function suggest its possible involvement in tumor progression. This hypothesis was tested using the 2G7 IgG2b, which neutralizes TGF-β1, -β2, and -β3, and the MDA-231 human breast cancer cell line. Inoculation of these cells in athymic mice decreases mouse spleen natural killer (NK) cell activity, Intraperitoneal injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing anti-TGF-β 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and control tumors were identical, Intraperitoneal administration of 2G7 resulted in a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231 primary tumor or metastases formation, nor did it stimulate NK cell-mediated cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned medium from MDA-231 cells inhibited the NK cell activity of human blood lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-β 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF-β in the progression of mammary carcinomas by suppressing host immune surveillance.
AB - TGF-β effects on angiogenesis, stroma formation, and immune function suggest its possible involvement in tumor progression. This hypothesis was tested using the 2G7 IgG2b, which neutralizes TGF-β1, -β2, and -β3, and the MDA-231 human breast cancer cell line. Inoculation of these cells in athymic mice decreases mouse spleen natural killer (NK) cell activity, Intraperitoneal injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing anti-TGF-β 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and control tumors were identical, Intraperitoneal administration of 2G7 resulted in a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231 primary tumor or metastases formation, nor did it stimulate NK cell-mediated cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned medium from MDA-231 cells inhibited the NK cell activity of human blood lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-β 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF-β in the progression of mammary carcinomas by suppressing host immune surveillance.
KW - Breast neoplasms
KW - Immunologic surveillance
KW - Natural killer activity
KW - Nude mice
KW - Transforming growth factor-β
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M3 - Article
C2 - 7504687
AN - SCOPUS:0027137485
SN - 0021-9738
VL - 92
SP - 2569
EP - 2576
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -