Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.
Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.
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DOI：
10.1002/path.4172
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发表时间：
2013-05
影响因子：
7.3
通讯作者：
Kocher, Hemant M.
中科院分区：
文献类型：
--
作者：
Kadaba, Raghu;Birke, Hanna;Wang, Jun;Hooper, Steven;Andl, Claudia D.;Di Maggio, Francesco;Soylu, Erdinc;Ghallab, Mohammed;Bor, Daniel;Froeling, Fieke E. M.;Bhattacharya, Satyajit;Rustgi, Anil K.;Sahai, Erik;Chelala, Claude;Sasieni, Peter;Kocher, Hemant M.
与相应的肿瘤相比，上皮组织具有稀疏的间质。癌细胞对基质细胞的影响是公认的。越来越多的基质成分，如内皮细胞和免疫细胞，被认为是癌症进展不可或缺的。相反，促结缔组织增生间质的作用却知之甚少。靶向肿瘤内的这些细胞成分是有吸引力的。最近的证据有力地指出，动态基质细胞参与癌症进展，影响患者的预后。在生物工程、拟生理器官型培养物和回归分析中研究了特定促纤维增生基质细胞（如胰腺癌、食管癌和皮肤癌中的星状细胞和肌成纤维细胞）的作用。对于胰腺癌，当间质（胰腺星状细胞）细胞构成细胞群的大部分时（在0.66-0.83的间质细胞比例下的最大效应），伴随着关键分子（如E-钙粘蛋白和β-连环蛋白）表达的变化，发生对增加癌细胞增殖和侵袭以及减少癌细胞凋亡的最大效应。跨三种肿瘤类型的基因表达微阵列表明，基质细胞一致且显著地改变了整体癌细胞功能，如细胞周期、细胞-细胞信号传导、细胞运动、细胞死亡和炎症反应。然而，这些变化是通过癌症类型特异性表达改变介导的，在肿瘤类型中几乎没有共同的靶点。正如这些体外数据所强调的，在体内，可以显示癌细胞中E-钙粘蛋白和多聚免疫球蛋白受体（PIGR）表达的相互关系取决于人胰腺癌的基质含量。这些研究表明，背景特异性癌症-间质串扰需要精确定义以实现有效的治疗靶向。这些数据可能与上皮细胞与基质细胞相互作用的非恶性过程有关，例如慢性炎症和纤维化状况。
Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66–0.83), accompanied by change in expression of key molecules such as E-cadherin and β-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell–cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer–stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.
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聚合免疫球蛋白受体在人肝细胞癌炎症诱导的肿瘤转移中的作用。
DOI：
10.1093/jnci/djr360
发表时间：
2011-11-16
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Ai J;Tang Q;Wu Y;Xu Y;Feng T;Zhou R;Chen Y;Gao X;Zhu Q;Yue X;Pan Q;Xu S;Li J;Huang M;Daugherty-Holtrop J;He Y;Xu HE;Fan J;Ding J;Geng M
通讯作者：
Geng M
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
29.4
作者：
Froeling, Fieke E. M.;Feig, Christine;Kocher, Hemant M.
通讯作者：
Kocher, Hemant M.
影响因子：
29.4
作者：
Bachem, MG;Schneider, E;Adler, G
通讯作者：
Adler, G
影响因子：
11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.