PT  - JOURNAL ARTICLE
AU  - FREDIKA M. ROBERTSON
AU  - SUSAN R. MALLERY
AU  - VALERIE K. BERGDALL-COSTELL
AU  - MARK (MING-CHENG) CHENG
AU  - PING PEI
AU  - JENIFER R. PROSPERI
AU  - MAURO FERRARI
TI  - Cyclooxygenase-2 Directly Induces MCF-7 Breast Tumor Cells to Develop into Exponentially Growing, Highly Angiogenic and Regionally Invasive Human Ductal Carcinoma Xenografts
DP  - 2007 Mar 01
TA  - Anticancer Research
PG  - 719--727
VI  - 27
IP  - 2
4099  - http://ar.iiarjournals.org/content/27/2/719.short
4100  - http://ar.iiarjournals.org/content/27/2/719.full
SO  - Anticancer Res2007 Mar 01; 27
AB  - 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 5×106 tumor cells into mammary fat pads of ovariectomized female Crl:Nu-Foxn1nu mice implanted with slow release 17-β 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-Foxn1nu 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. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved