TY  - JOUR
TI  - Non-steroidal anti-inflammatory drugs target the pro-tumorigenic extracellular matrix of the postpartum mammary gland
AU  - O’Brien, Jenean
AU  - Hansen, Kirk
AU  - Barkan, Dalit
AU  - Green, Jeffrey
AU  - Schedin, Pepper
AU  - O'Brien, Jenean
AU  - Hansen, Kirk
AU  - Barkan, Dalit
AU  - Green, Jeffrey
AU  - Schedin, Pepper
T2  - The International Journal of Developmental Biology
AB  - 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.
PY  - 2011
DO  - 10.1387/ijdb.113379jo
VL  - 55
IS  - 7-8-9
SP  - 745
EP  - 755
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/113379jo
Y2  - 2024/05/05/20:37:28
ER  -