Rat Mammary Extracellular Matrix Composition and Response to Ibuprofen Treatment During Postpartum Involution by Differential GeLC鈥揗S/MS Analysis

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• 作者：Jenean H. O鈥橞rien ; Lauren A. Vanderlinden ; Pepper J. Schedin ; Kirk C. Hansen
• 刊名：Journal of Proteome Research
• 出版年：2012
• 出版时间：October 5, 2012
• 年：2012
• 卷：11
• 期：10
• 页码：4894-4905
• 全文大小：540K
• 年卷期：v.11,no.10(October 5, 2012)
• ISSN：1535-3907

文摘

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鈥揗S/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-伪1 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.

Keywords:

cs.org/action/doSearch?action=search&searchText=cancer+biology&qsSearchArea=searchText">cancer biology; cs.org/action/doSearch?action=search&searchText=extracellular+matrix&qsSearchArea=searchText">extracellular matrix; cs.org/action/doSearch?action=search&searchText=protein+identification&qsSearchArea=searchText">protein identification; cs.org/action/doSearch?action=search&searchText=quantification&qsSearchArea=searchText">quantification; cs.org/action/doSearch?action=search&searchText=tumor+microenvironment&qsSearchArea=searchText">tumor microenvironment; cs.org/action/doSearch?action=search&searchText=stroma&qsSearchArea=searchText">stroma