Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche.
Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche.
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肿瘤内基质细胞中的骨膜蛋白表达通过创建癌症支持性生态位来预测结直肠癌
DOI：
10.18632/oncotarget.5985
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发表时间：
2016-01-05
期刊：
影响因子：
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通讯作者：
Cao G
中科院分区：
文献类型：
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作者：
Xu X;Chang W;Yuan J;Han X;Tan X;Ding Y;Luo Y;Cai H;Liu Y;Gao X;Liu Q;Yu Y;Du Y;Wang H;Ma L;Wang J;Chen K;Ding Y;Fu C;Cao G
癌细胞和循环中的骨膜蛋白（POSTN）表达与结直肠癌（CRC）的不良预后有关。然而，在肿瘤内基质中表达的POR 4在CRC进展中的作用在很大程度上仍然未知。本研究纳入了1098例在中国大陆上海和广州接受手术治疗的CRC患者。在多变量考克斯模型中，经TNM分期和术后化疗等协变量校正后，上海队列中，间质POSTs表达评分从癌旁黏膜、原发结直肠癌组织到转移结直肠癌组织依次升高（P < 0.001），而中、高表达的间质POSTs，而非上皮POSTs，独立预测结直肠癌的不良预后。上海队列的结果在广州队列中得到了忠实的复制。基质过氧化物酶表达剂量依赖性地预测了两组术后化疗的III期CRC患者的不良预后。来源于结肠成纤维细胞的POR 4或重组POR 4显著促进CRC细胞的增殖、锚定非依赖性生长、侵袭和化疗抗性;而这些作用通过靶向PI 3 K/Akt或Wnt/β-catenin信号通路而被抵消。CRC细胞RKO衍生因子显著诱导结肠成纤维细胞中的过氧化物酶产生，并且自分泌过氧化物酶促进成纤维细胞的增殖、迁移和锚定非依赖性生长。结论是，间质POL 4通过创造一个促进癌症进展的小生境，对CRC具有预后和预测作用。靶向POSTN诱导的信号通路可能是转移性或化疗耐药CRC的治疗选择。
Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC.
影响因子：
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作者：
Allen JE;El-Deiry WS
通讯作者：
El-Deiry WS