Home LiteratureArticle Details
PMID: 21822285 Published · epublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Nature medicine ·Vol. 17 ·No. 9 ·2011-08-07 ·Pages 1109-15

Lyons TR, O'Brien J, Borges VF, Conklin MW, Keely PJ, Eliceiri KW, Marusyk A, Tan AC, Schedin P

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.

MeSH Terms
Analysis of Variance Animals Blotting, Western Breast Neoplasms/drug therapy,physiopathology Carcinoma, Ductal/drug therapy,physiopathology Celecoxib Cell Line, Tumor Cyclooxygenase 2/metabolism Disease Models, Animal Female Fibrillar Collagens/metabolism Humans Ibuprofen/pharmacology,therapeutic use Immunohistochemistry In Situ Hybridization, Fluorescence Mammary Glands, Animal/drug effects,metabolism,physiology Mice Mice, SCID Neoplasm Invasiveness/physiopathology Postpartum Period/drug effects,physiology Pregnancy Pyrazoles/pharmacology,therapeutic use Reverse Transcriptase Polymerase Chain Reaction Sulfonamides/pharmacology,therapeutic use
Chemicals
Fibrillar Collagens Pyrazoles Sulfonamides Ptgs2 protein, mouse Cyclooxygenase 2 Celecoxib Ibuprofen
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lyons Traci R
Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
O'Brien Jenean
Borges Virginia F
Conklin Matthew W
Keely Patricia J
Eliceiri Kevin W
Marusyk Andriy
Tan Aik-Choon
Schedin Pepper
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.2416
Published
2011-08-07
Epub
2011-00-07
Pages
1109-15
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC3888478
Subset
IM
Grants
NCI NIH HHS · P30 CA046934 · United States
NCI NIH HHS · R01 CA114462 · United States
NCI NIH HHS · R01 CA136590 · United States
NCI NIH HHS · R01 CA142833 · United States
External Links
PubMed source DOI: 10.1038/nm.2416 PMC Full Text View journal details
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