Antitumor/antiestrogenic effect of the chemokine interferon inducible protein 10 (IP-10) involves suppression of VEGF expression in mammary tissue.
Vascular endothelial growth factor (VEGF) promotes angiogenesis in a number of tumor model systems. We reported previously that estrogen supports the growth of CCL-51 cell-based mammary tumors in mice, which could be blocked with specific chemokines. We investigated whether promotion of tumor growth by estrogen, and suppression of tumor growth by chemokines, was associated with VEGF protein expression. Female C3H mice were treated with vehicle, estradiol, or with one of several chemokines for 72 h. The presence of VEGF in mammary tissue samples was detected and quantified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting using antimurine VEGF antibodies. Estrogen significantly increased mammary VEGF expression. Cotreatment with tamoxifen or the chemokine interferon-inducible protein-10 (IP-10) suppressed the action estrogen on VEGF expression. CCL-51 tumor cells were placed into mammary tissue of C3H mice. Mice were treated every 72-h with either vehicle or estradiol, in the presence or absence of IP-10 for 21 days. Estrogen supported CCL-51 tumor growth, with an average of 2.3 tumors present/animal. Cotreatment of mice with estrogen and IP-10 resulted in significantly lower numbers of tumors in mammary tissue in comparison to animals treated with estrogen alone. VEGF levels in mammary tissue and tumors of IP-10 and estrogen cotreated mice were 40-50% less than those detected in mammary tissue of estrogen-treated mice. Our results suggest that estrogenic support of CCL-51 mammary tumor growth is related to increased VEGF expression, and that the inhibitory action of IP-10 may be related to suppressing VEGF levels in mammary tissue.
Aronica
Susan M
SM
Department of Biology, Canisius College, Buffalo, New York 14208, USA. aronicas@canisius.edu
Raiber
Lisa
L
Hanzly
Michael
M
Kisela
Caroline
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D004965:Estrogen Antagonists; D004967:Estrogens; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen