Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC–MS/MS analysis

JH O'Brien, LA Vanderlinden, PJ Schedin… - Journal of proteome …, 2012 - ACS Publications
JH O'Brien, LA Vanderlinden, PJ Schedin, KC Hansen
Journal of proteome research, 2012ACS Publications
Breast cancer patients diagnosed within five years following pregnancy have increased
metastasis and decreased survival. A hallmark of postpartum biology that may contribute to
this poor prognosis is mammary gland involution, involving massive epithelial cell death and
dramatic stromal remodeling. Previous studies show pro-tumorigenic properties of
extracellular matrix (ECM) isolated from rodent mammary glands undergoing postpartum
involution. More recent work demonstrates systemic ibuprofen treatment during involution …
Breast cancer patients diagnosed within five years following pregnancy have increased metastasis and decreased survival. A hallmark of postpartum biology that may contribute to this poor prognosis is mammary gland involution, involving massive epithelial cell death and dramatic stromal remodeling. Previous studies show pro-tumorigenic properties of extracellular matrix (ECM) isolated from rodent mammary glands undergoing postpartum involution. More recent work demonstrates systemic ibuprofen treatment during involution decreases its tumor-promotional nature. Utilizing a proteomics approach, we identified relative differences in the composition of mammary ECM isolated from nulliparous rats and those undergoing postpartum involution, with and without ibuprofen treatment. GeLC–MS/MS experiments resulted in 20327 peptide identifications that mapped to 884 proteins with a <0.02% false discovery rate. Label-free quantification yielded several ECM differences between nulliparous and involuting glands related to collagen-fiber organization, cell motility and attachment, and cytokine regulation. Increases in known pro-tumorigenic ECM proteins osteopontin, tenascin-C, and laminin-α1 and pro-inflammatory proteins STAT3 and CD68 further identify candidate mediators of breast cancer progression specific to the involution window. With postpartum ibuprofen treatment, decreases in tenascin-C and three laminin chains were revealed. Our data suggest novel ECM mediators of breast cancer progression and demonstrate a protective influence of ibuprofen on mammary ECM composition.
ACS Publications