Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7
Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7
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DOI：
10.1002/ijc.25060
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发表时间：
2010-07-15
影响因子：
6.4
通讯作者：
Kim, Jin
中科院分区：
文献类型：
--
作者：
Jung, Da-Woon;Che, Zhong Min;Kim, Jin
最近的研究表明，基质成纤维细胞对癌症的发生和进展的影响比以前认识的更为深远。本研究旨在研究口腔鳞状细胞癌（OSCC）中癌细胞及其相关成纤维细胞在分子和细胞水平上的相互关系。为了识别癌症相关成纤维细胞 (CAF) 表达的促进癌细胞侵袭的关键分子调节因子，通过将共培养的 OSCC 细胞和 CAF 与单一培养对照进行比较，进行了微阵列分析。微阵列和实时 PCR 分析发现共培养的 CAF 中趋化因子（C-C 基序）配体 7 (CCL7) 显着上调。 ELISA 显示与 OSCC 细胞共培养刺激的 CAF 的 CCL7 分泌水平升高。 CCL7促进OSCC细胞的侵袭和迁移，CCL7中和抗体处理可抑制侵袭性。 RT-PCR 显示 OSCC 细胞表达 CCR1、CCR2 和 CCR3（CCL7 受体）。此外，用抗CCR1或抗CCR3抗体治疗可抑制CCL7诱导的OSCC细胞迁移，这表明CCL7通过CCR1和CCR3促进OSCC细胞上的癌细胞迁移。对 OSCC 细胞培养物上清液的细胞因子抗体阵列分析表明，白介素-1α 是 CAF 分泌 CCL7 的诱导剂。这项研究证实了调节 OSCC 侵袭的分子串扰的相互关系，并描述了未来治疗的新的潜在靶点。
Recent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real-time PCR analysis identified marked upregulation of the chemokine (C-C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT-PCR. In addition, treatment with anti-CCR1 or anti-CCR3 antibody inhibited CCL7-induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin-la was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy.