Androgen receptor influences the invasion and metastasis in prostate cancer molecular biological study

我们建立了一株稳定转染雄激素受体cDNA的克隆性前列腺癌细胞（DU-145/AR）。1：雄激素受体（雄激素受体，AR）可能通过影响特异性整合素亚基的表达，参与调控前列腺癌细胞对细胞外基质的粘附和侵袭。2：与DU-145/AR细胞相比，DU-145细胞选择性高水平表达CXCR4和CCR1 mRNA。DU-145对其配体CXCL12和CCL3表现出强烈的迁移反应。相比之下，CXCL12和CCL3均不影响DU-145/AR细胞的迁移。这些结果表明，AR的表达通过趋化因子及其受体系统下调人前列腺癌细胞的迁移反应。3: 94%的转移性前列腺癌患者活检标本中检测到CXCR4。CXCR4的表达与病理分级、骨转移程度或激素治疗的临床反应无关。肿瘤中强表达CXCR4的患者比弱表达CXCR4的患者的病因特异性生存率更低。多因素分析显示，CXCR4表达和病理分级是影响预后的重要因素。免疫组织化学染色检测的CXCR4含量被认为是转移性前列腺癌患者接受雄激素停药治疗的一个有用的预后因素。4：前列腺癌细胞和前列腺上皮细胞表达HGF激活因子抑制剂类型1 (HAI-1)，而前列腺基质细胞不表达。可溶型HAI-1在上清液中的表达结果相同。雄激素影响部分前列腺细胞系中HAI-1的表达。

We have established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor cDNA.1: Androgen receptor (AR) may play a role in the regulation of adhesion to the extracellular matrices and invasion of prostate cancer cells by influencing the expression of specific integrin subunits.2: DU-145 cells selectively expressed CXCR4 and CCR1 mRNA at high levels compared with DU-145/AR cells. DU-145 showed vigorous migratory responses to its ligand CXCL12 and CCL3. In contrast, neither CXCL12 nor CCL3 affected the migration of DU-145/AR cells. These results indicate that expression of AR down-regulates the migratory responses of human prostate cancer cells via chemokine and its receptor systems.3: CXCR4 was detected in 94% of the biopsy specimens from patients with metastatic prostate cancer. CXCR4 expression showed no association with the pathological grade, extent of bony metastasis, or clinical response to hormonal therapy. Patients with a strong expression of CXCR4 in tumors revealed poorer cause-specific survival than those with a weak expression of CXCR4. Multivariate analysis showed that CXCR4 expression and pathological grade were significant prognostic factors. The CXCR4 content assayed using immunohistochemical staining was considered to be a useful prognostic factor for patients with metastatic prostate cancer treated with androgen withdrawal therapy.4: Prostate cancer cell and prostate epithelial cell expressed HGF activator inhibitor type1 (HAI-1), but prostate stromal cell did not. The soluble-type HAI-1 expression in the supernatant showed the same result. Androgen influenced the expression of HAI-1 in some prostate cell lines.