Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion
Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion
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TGF-β1 对癌相关成纤维细胞中细胞外基质蛋白表达的差异调节可调节癌细胞扩散，但不调节粘附
DOI：
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
O. De Wever
中科院分区：
文献类型：
--
作者：
M. V. van Bockstal;K. Lambein;M. Van Gele;Elly De Vlieghere;Ridha Limame;G. Braems;R. Van den Broecke;V. Cocquyt;H. Denys;M. Bracke;L. Libbrecht;O. De Wever
肿瘤进展的特征在于肿瘤上皮和相邻基质细胞之间复杂的相互作用。在乳腺导管原位癌（DCIS）中，间质核心蛋白聚糖表达减少和粘液样间质与复发风险增加相关。在这项研究中，我们的目的是探讨旁分泌调控核心蛋白聚糖和相关的细胞外基质（ECM）蛋白在癌相关成纤维细胞（CAFs）的表达。转化生长因子-β1（TGF-β1）被鉴定为一种有效的ECM调节剂，因为它减少核心蛋白聚糖并强烈增强多功能蛋白聚糖、双糖蛋白聚糖和I型胶原蛋白的表达。当用碱性成纤维细胞生长因子（bFGF）处理成纤维细胞时，观察到类似但不太明显的效果。尽管这种一致的ECM调节，TGF-β1和bFGF差异调节α-平滑肌肌动蛋白（α-SMA）的表达，这通常被认为是一种CAF标记物。癌细胞来源的分泌体诱导成纤维细胞中多功能蛋白聚糖和双糖蛋白聚糖的表达。20例DCIS标本的免疫组化显示，在粘液样间质的DCIS中，有导管周围多功能蛋白聚糖过表达的趋势。核心蛋白聚糖抑制癌细胞粘附，但不抑制CAF衍生的基质。当将癌细胞接种在来自TGF-β1处理的CAF的基质上时，癌细胞呈现显著增强的扩散。总之，这些数据表明，浸润前的癌性病变可能通过TGF-β1的释放来调节周围基质的组成，以获得允许浸润的微环境。
Cancer progression is characterized by a complex reciprocity between neoplastic epithelium and adjacent stromal cells. In ductal carcinoma in situ (DCIS) of the breast, both reduced stromal decorin expression and myxoid stroma are correlated with increased recurrence risk. In this study, we aimed to investigate paracrine regulation of expression of decorin and related extracellular matrix (ECM) proteins in cancer-associated fibroblasts (CAFs). Transforming growth factor-β1 (TGF-β1) was identified as a competent ECM modulator, as it reduced decorin and strongly enhanced versican, biglycan and type I collagen expression. Similar but less pronounced effects were observed when fibroblasts were treated with basic fibroblast growth factor (bFGF). Despite this concerted ECM modulation, TGF-β1 and bFGF differentially regulated alpha-smooth muscle actin (α-SMA) expression, which is often proposed as a CAF-marker. Cancer cell-derived secretomes induced versican and biglycan expression in fibroblasts. Immunohistochemistry on twenty DCIS specimens showed a trend toward periductal versican overexpression in DCIS with myxoid stroma. Cancer cell adhesion was inhibited by decorin, but not by CAF-derived matrices. Cancer cells presented significantly enhanced spreading when seeded on matrices derived from TGF-β1-treated CAF. Altogether these data indicate that preinvasive cancerous lesions might modulate the composition of surrounding stroma through TGF-β1 release to obtain an invasion-permissive microenvironment.
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DOI：
10.1007/978-1-59745-413-1_19
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
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作者：
Castello-Cros, Remedios;Cukierman, Edna
通讯作者：
Cukierman, Edna
影响因子：
4.7
作者：
Ghosh S;Albitar L;LeBaron R;Welch WR;Samimi G;Birrer MJ;Berkowitz RS;Mok SC
通讯作者：
Mok SC
DOI：
10.1172/jci15333
发表时间：
2002-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Yu-an Yang;O. Dukhanina;Binwu Tang;M. Mamura;J. Letterio;Jennifer N Macgregor;S. C. Patel;S. Khozin;Zi-yao Liu;Jeffrey E. Green;M. Anver;G. Merlino;L. Wakefield
通讯作者：
Yu-an Yang;O. Dukhanina;Binwu Tang;M. Mamura;J. Letterio;Jennifer N Macgregor;S. C. Patel;S. Khozin;Zi-yao Liu;Jeffrey E. Green;M. Anver;G. Merlino;L. Wakefield
影响因子：
11.2
作者：
Lee S;Stewart S;Nagtegaal I;Luo J;Wu Y;Colditz G;Medina D;Allred DC
通讯作者：
Allred DC
乳腺癌细胞对基质多功能蛋白聚糖表达的调节以及对淋巴结阴性原发性乳腺癌患者无复发生存的重要性。
DOI：
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发表时间：
2002
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ricciardelli,Carmela;Brooks,JohnH;Suwiwat,Supaporn;Sakko,AndrewJ;Mayne,Keiko;Raymond,WendyA;Seshadri,Ram;LeBaron,RichardG;Horsfall,DavidJ
通讯作者：
Horsfall,DavidJ