Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P.R. China.
Oncol Rep. 2013 Oct;30(4):1920-8. doi: 10.3892/or.2013.2656. Epub 2013 Aug 5.
Tumor metastasis is one of the causes for the high mortality rate of prostate cancer (PCa) patients, yet the molecular mechanisms of PCa metastasis are not fully understood. In our previous studies, we found that PSMA suppresses the metastasis of PCa, yet the underlying mechanism remains unknown. To identify the genes related to tumor metastasis possibly regulated by PSMA, we performed tumor metastasis PCR array assay to analyze the differentially expressed tumor metastasis-related genes. Eighty-four tumor metastasis related genes were screened in si-PSMA LNCap cells (PSMA silenced by siRNA)/LNCap cells and in PC-3/LNcap cells, respectively. Expression levels of possible related genes were verified by real-time PCR in 4 prostate cancer cell lines (LNCap, 22RV1, PC-3 and DU145) and in 85 clinical samples (12 normal, 26 benign prostatic hypertrophy and 47 prostate cancer tissues). The results showed that 10 genes (including CDH6 and CXCL12) were upregulated and 4 genes (CCL7, ITGB3, MDM2 and MMP2) were downregulated in the si-PSMA LNCap cells. There were 41 genes significantly upregulated and 15 genes downregulated in PC-3 cells when compared with LNCap cells. Eight common genes were found in both the si-PSMA and PSMA(-) groups. CDH6, MMP3, MTSS1 were further identified as PSMA-related genes in the prostate cancer cell lines and clinical samples, and their expression showed a negative correlation with the stage of prostate cancer (P<0.0001) and PSMA level (P<0.05) in clinical samples, indicating their possible involvement in PSMA-related PCa metastasis regulation. These findings may provide insights into the mechanism involved in the suppression of PCa metastasis by PSMA and its possible interacting proteins, and may provide clues for further exploration of the molecular mechanism of PCa metastasis.
肿瘤转移是导致前列腺癌（PCa）患者死亡率高的原因之一，但 PCa 转移的分子机制尚不完全清楚。在我们之前的研究中，发现 PSMA 抑制 PCa 的转移，但潜在的机制尚不清楚。为了鉴定可能受 PSMA 调节的与肿瘤转移相关的基因，我们进行了肿瘤转移 PCR 阵列分析，以分析差异表达的肿瘤转移相关基因。在分别用 siRNA 沉默 PSMA 的 si-PSMA LNCap 细胞和 PC-3/LNcap 细胞中筛选了 84 个肿瘤转移相关基因。在 4 种前列腺癌细胞系（LNCap、22RV1、PC-3 和 DU145）和 85 个临床样本（12 个正常、26 个良性前列腺增生和 47 个前列腺癌组织）中通过实时 PCR 验证了可能相关基因的表达水平。结果显示，在 si-PSMA LNCap 细胞中，有 10 个基因（包括 CDH6 和 CXCL12）上调，4 个基因（CCL7、ITGB3、MDM2 和 MMP2）下调。与 LNCap 细胞相比，PC-3 细胞中有 41 个基因显著上调，15 个基因下调。在 si-PSMA 和 PSMA(-)组中发现了 8 个共同的基因。在前列腺癌细胞系和临床样本中，进一步鉴定 CDH6、MMP3、MTSS1 为 PSMA 相关基因，其表达与前列腺癌的分期（P<0.0001）和临床样本中的 PSMA 水平（P<0.05）呈负相关，表明它们可能参与 PSMA 相关的 PCa 转移调节。这些发现可能为 PSMA 抑制 PCa 转移及其可能的相互作用蛋白的机制提供新的认识，并为进一步探索 PCa 转移的分子机制提供线索。
