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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | O'Brien, Jenean Hansen, Kirk Barkan, Dalit Green, Jeffrey Schedin, Pepper |
| Description | Country affiliation: United States Author Affiliation: O'Brien J ( School of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, Aurora, CO, USA.) |
| Abstract | Breast cancer patients diagnosed postpartum have poor prognosis. The postpartum mammary gland undergoes tissue regression to return to the pre-pregnant state. This involution is characterized by wound healing programs known to be tumor promotional in other contexts. Previous studies have shown that mammary extracellular matrix (ECM) from nulliparous rats has tumor suppressive attributes, while mammary ECM from involuting mammary glands is promotional. In models of pregnancy-associated breast cancer, non-steroidal anti-inflammatory drug (NSAID) treatment targeted to postpartum involution inhibits tumor progression, in part by suppressing COX-2 dependent collagen deposition. Because mammary ECM proteins are coordinately regulated, NSAID treatment is anticipated to result in additional protective changes in the mammary extracellular matrix. Here, systemic NSAID treatment was utilized during postpartum involution to reduce mammary COX-2 activity. ECM was isolated from actively involuting glands of rats treated with NSAIDs and compared to ECM isolated from control-involution and nulliparous rats in 3D cell culture and xenograft assays. Compositional changes in ECM between groups were identified by proteomics. In four distinct 3D culture assays, normal and transformed mammary epithelial cells plated in NSAID-involution ECM, phenocopied cells plated in ECM from nulliparous rats rather than ECM from control-involution rats. Tumor cells mixed with NSAID-involution ECM and injected orthotopically in mice formed smaller tumors than cells mixed with control-involution ECM. Proteomic analyses identified and 3D culture assays implicated the ECM protein tenascin-C as a potential mediator of tumor progression during involution that is decreased by NSAID treatment. In summary, NSAID treatment decreases tumor-promotional attributes of postpartum involution mammary ECM. |
| File Format | HTM / HTML |
| ISSN | 02146282 |
| e-ISSN | 16963547 |
| Journal | The International Journal of Developmental Biology |
| Issue Number | 7-9 |
| Volume Number | 55 |
| Language | English |
| Publisher | University of the Basque Country Press |
| Publisher Date | 2011-01-01 |
| Publisher Place | Spain |
| Access Restriction | Open |
| Subject Keyword | Discipline Embryology Discipline Biology Anti-inflammatory Agents, Non-steroidal Pharmacology Mammary Neoplasms, Experimental Prevention & Control Postpartum Period Drug Effects Animals Carcinogens Metabolism Cell Line, Tumor Cyclooxygenase 2 Extracellular Matrix Mammary Glands, Animal Pathology Etiology Mice Pregnancy Rats, Sprague-dawley Tenascin Research Support, N.i.h., Extramural Research Support, N.i.h., Intramural Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Developmental Biology Embryology |
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