1. Cyclooxygenase-2 directly induces MCF-7 breast tumor cells to develop into exponentially growing, highly angiogenic and regionally invasive human ductal carcinoma xenografts.
- Author
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Robertson FM, Mallery SR, Bergdall-Costell VK, Cheng M, Pei P, Prosperi JR, and Ferrari M
- Subjects
- Animals, Breast Neoplasms blood supply, Breast Neoplasms genetics, Breast Neoplasms pathology, Carcinoma, Ductal, Breast blood supply, Carcinoma, Ductal, Breast genetics, Carcinoma, Ductal, Breast pathology, Cell Growth Processes physiology, Cell Line, Tumor, Cyclooxygenase 2 biosynthesis, Cyclooxygenase 2 genetics, Female, Humans, Immunohistochemistry, Lymphatic Metastasis, Mice, Mice, Nude, Neoplasm Invasiveness, Neoplasm Transplantation, Neovascularization, Pathologic enzymology, Neovascularization, Pathologic pathology, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Transfection, Transplantation, Heterologous, Breast Neoplasms enzymology, Carcinoma, Ductal, Breast enzymology, Cyclooxygenase 2 metabolism
- Abstract
Based on our studies demonstrating first time evidence that the cyclooxygenase-2 (Cox-2) enzyme is abundant within invasive human breast tumors, we developed a clonally derived human breast tumor cell clone designated as MCF-7/Cox-2 Clone 10 by transfection of human Cox-2 cDNA into slow growing, Cox-2 null, non-metastatic MCF-7 human breast tumor cells. The present studies evaluated the biological characteristics of the MCF-7/Cox-2 Clone 10 human breast tumors compared to the characteristics of MCF-7/empty vector control tumors when grown in vivo following injection of 5x10(6) tumor cells into mammary fat pads of ovariectomized female Crl:Nu-Foxn1(nu) mice implanted with slow release 17-beta estradiol pellets. At 60 days after tumor cell injection, MCF-7/Cox-2 Clone 10 human breast tumors were 4-fold greater (p < 0.01) in volume than MCF-7/empty vector control tumors. MCF-7/Cox-2 Clone 10 human breast tumor xenografts were highly angiogenic based on histological observation of large-bore blood vessels, which was confirmed by immunohistochemical staining with anti-CD-31 antibody and quantitation of mean vessel density. MCF-7/Cox-2 Clone 10 human breast tumor cells were present within regional lymph nodes adjacent to mammary fat pads with their local invasion confirmed by Western blotting of Cox-2-protein. This unique Cox-2-dependent breast tumor model rapidly produces large, angiogenic, locally invasive human breast tumor xenografts in mammary fat pads of ovariectomized female Crl:Nu-Foxn1(nu) mice at 42-60 days which recapitulate human breast ductal carcinomas. This unique model may be invaluable as a means to evaluate preclinical safety and efficacy of novel adjuvant therapies for women with metastastic breast cancer including prostanoid receptor antagonists, newly developed anti-angiogenic therapies, as well as other novel approaches for targeting and destruction of human breast tumors and their vasculature.
- Published
- 2007