BACKGROUND Stromal-derived CXCL12 play an important role which influence the proliferation and invasiveness of colon cancer in microenvironment. The present study aimed to analyze the underlying mechanism by which CXCL12 and tumour suppressor protein phosphatase and tensin homologue deleted on chromosome 10 (PTEN) influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS RT-PCR and western blot were detected the expression of CXCL12, CXCR4 and PTEN in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and PTEN on proliferation and invasion of colon cancer cells were evaluated by real-time PCR, proliferation and invasion assays using an in vitro system consisting of co-cultured cancer cells and stromal cells. We eventually investigated activation of PI3K/Akt signaling by CXCL12 regulate PTEN and involved in the metastatic process of colon cancer. In addition, we also examine how the knockdown of PTEN influences proliferation and invasion and correlate with CXCL12/CXCR4/PI3K/Akt, determination of PTEN up-down-stream targets that preferentially contribute to tumorigenesis. RESULTS Blockage of PTEN phosphorylation led to a stronger enhancement of cell proliferation and invasion upon stimulation with CXCL12 via its activation of the PI3K/Akt signaling pathway. Furthermore, knockdown of PTEN by siRNA transfection was also found to enhance the activation of the PI3K/Akt pathway, thereby promoting cell invasion and proliferation. CXCL12 induced transcriptional down-regulation of activated PTEN and this signaling pathway promotes cell survival. CXCL12/CXCR4/PI3K/Akt cascade may be critical for colon cancer cells to metastasize. CONCLUSIONS Based on our results, we suggest that the modification of CXCR4, PTEN, or PI3K function might be promising new therapeutic approaches to inhibit the aggressive spread of colon cancer.

中文翻译：

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成纤维细胞衍生的CXCL12调节PTEN表达，并通过PI3k / Akt信号传导与结肠癌细胞的增殖和侵袭有关。

背景技术基质来源的CXCL12在影响微环境中结肠癌的增殖和侵袭性中起着重要的作用。本研究旨在分析在第10号染色体（PTEN）上缺失的CXCL12和肿瘤抑制蛋白磷酸酶和张力蛋白同源物影响结肠癌转移潜力以及结肠癌与基质细胞内部关系的潜在机制。方法采用RT-PCR和western blot方法检测结肠癌细胞和基质细胞中CXCL12，CXCR4和PTEN的表达。通过实时PCR，增殖和侵袭测定法，使用由共培养的癌细胞和基质细胞组成的体外系统，评估了CXCL12和PTEN对结肠癌细胞增殖和侵袭的协同作用。我们最终研究了通过CXCL12调节PTEN激活PI3K / Akt信号传导并参与结肠癌的转移过程。此外，我们还研究了PTEN的敲低如何影响增殖和侵袭并与CXCL12 / CXCR4 / PI3K / Akt相关联，确定优先有助于肿瘤发生的PTEN下游靶标。结果PTEN磷酸化的阻断通过激活PI3K / Akt信号通路，在用CXCL12刺激后，导致细胞增殖和侵袭的增强。此外，还发现通过siRNA转染敲低PTEN可增强PI3K / Akt途径的活化，从而促进细胞侵袭和增殖。CXCL12诱导了激活的PTEN的转录下调，并且该信号通路促进了细胞存活。CXCL12 / CXCR4 / PI3K / Akt级联对于结肠癌细胞的转移可能至关重要。结论基于我们的研究结果，我们认为CXCR4，PTEN或PI3K功能的修饰可能是抑制结肠癌侵袭性扩散的有前途的新治疗方法。