Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC-MS/MS analysis.
Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC-MS/MS analysis.
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DOI：
10.1021/pr3003744
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发表时间：
2012-10-05
影响因子：
4.4
通讯作者：
Hansen KC
中科院分区：
文献类型：
--
作者：
O'Brien JH;Vanderlinden LA;Schedin PJ;Hansen KC
怀孕后五年内诊断的乳腺癌患者转移增加，生存率下降。可能导致这种不良预后的产后生物学标志是乳腺退化，涉及大量上皮细胞死亡和戏剧性的基质重塑。先前的研究表明，从经历产后退化的啮齿动物乳腺中分离的细胞外基质（ECM）具有促肿瘤发生的特性。最近的研究表明，在退化过程中全身布洛芬治疗降低了其肿瘤促进性质。利用蛋白质组学方法，我们确定了从未经产大鼠和那些经历产后退化，有和没有布洛芬治疗的乳腺ECM的组成的相对差异。GeLC-MS/MS实验得到20，327个肽鉴定，映射到884个蛋白质，错误发现率<0.02%。无标记定量产生了一些ECM之间的差异，未经生产和退化的腺体有关的胶原纤维组织，细胞运动和附着，细胞因子的调节。已知的促肿瘤发生ECM蛋白骨桥蛋白、生腱蛋白-C和层粘连蛋白-α1以及促炎蛋白STAT 3和CD 68的增加进一步鉴定了对退化窗特异的乳腺癌进展的候选介质。产后布洛芬治疗，腱生蛋白-C和三个层粘连蛋白链的减少被揭示。我们的数据表明乳腺癌进展的新ECM介质，并证明布洛芬对乳腺ECM成分的保护作用。
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 composition of mammary ECM isolated from nulliparous rats and those undergoing postpartum involution, with and without ibuprofen treatment. GeLC-MS/MS experiments resulted in 20,327 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.
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影响因子：
8.4
作者：
Ioachim, E;Charchanti, A;Pavlidis, N
通讯作者：
Pavlidis, N
影响因子：
3.2
作者：
Amenta, PS;Scivoletti, NA;Myers, JC
通讯作者：
Myers, JC
影响因子：
7
作者：
Hansen, Kirk C.;Kiemele, Lauren;Schedin, Pepper
通讯作者：
Schedin, Pepper
影响因子：
11.2
作者：
Gupta, Piyush B.;Proia, David;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
DOI：
10.1016/s0304-4165(00)00158-6
发表时间：
2000-12-15
影响因子：
3
作者：
Geffrotin, C;Horak, V;Vielh, P
通讯作者：
Vielh, P