Cyclooxygenase-2 directly induces MCF-7 breast tumor cells to develop into exponentially growing, highly angiogenic and regionally invasive human ductal carcinoma xenografts

Fredika M. Robertson, Susan R. Mallery, Valerie K. Bergdall-Costell, Mark Cheng, Ping Pei, Jenifer R. Prosperi, Mauro Ferrari

Research output: Contribution to journalArticle

15 Scopus citations

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 infection 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.

Original languageEnglish (US)
Pages (from-to)719-727
Number of pages9
JournalAnticancer Research
Volume27
Issue number2
StatePublished - Mar 1 2007
Externally publishedYes

Keywords

  • Angiogenesis
  • Cyclooxygenase-2
  • Ductal carcinoma
  • Human breast cancer model
  • Invasion
  • MCF-7/Cox-2 Clone 10
  • Xenografts

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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