Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2

Traci R. Lyons, Jenean O'Brien, Virginia F. Borges, Matthew W. Conklin, Patricia J. Keely, Kevin W. Eliceiri, Andriy Marusyk, Aik Choon Tan, Pepper Schedin

Research output: Contribution to journalArticle

197 Scopus citations

Abstract

The prognosis of breast cancer in young women is influenced by reproductive history. Women diagnosed within 5 years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. Here we describe a mouse model of postpartum breast cancer that identifies mammary gland involution as a driving force of tumor progression. In this model, human breast cancer cells exposed to the involuting mammary microenvironment form large tumors that are characterized by abundant fibrillar collagen, high cyclooxygenase-2 (COX-2) expression and an invasive phenotype. In culture, tumor cells are invasive in a fibrillar collagen and COX-2-dependent manner. In the involuting mammary gland, inhibition of COX-2 reduces the collagen fibrillogenesis associated with involution, as well as tumor growth and tumor cell infiltration to the lung. These data support further research to determine whether women at high risk for postpartum breast cancer would benefit from treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) during postpartum involution.

Original languageEnglish (US)
Pages (from-to)1109-1116
Number of pages8
JournalNature medicine
Volume17
Issue number9
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lyons, T. R., O'Brien, J., Borges, V. F., Conklin, M. W., Keely, P. J., Eliceiri, K. W., Marusyk, A., Tan, A. C., & Schedin, P. (2011). Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nature medicine, 17(9), 1109-1116. https://doi.org/10.1038/nm.2416