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

我们建立了稳定表达雄激素受体cDNA1的前列腺癌DU-145细胞株(DU-145/AR)。1.雄激素受体(AR)可能通过影响特异性整合素亚基的表达，在调节细胞与细胞外基质的黏附和侵袭中发挥作用。2：与DU-145/AR细胞相比，DU-145细胞选择性高表达CXCR4和CCR1mRNA。DU-145对其配体CXCL12和CCL3表现出强烈的迁移反应。相反，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了人前列腺癌细胞的迁移反应。3：94%的转移性前列腺癌患者的活检标本中检测到CXCR4。CXCR4的表达与肿瘤的病理分级、骨转移程度或激素治疗的临床反应无关。在肿瘤中CXCR4强表达的患者比那些CXCR4弱表达的患者显示出更差的病因特定生存率。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CXCR4含量可作为转移性前列腺癌患者雄激素撤除治疗的预后指标。4：前列腺癌和前列腺上皮细胞表达HGF激活物抑制物1(HAI-1)，而前列腺癌间质细胞不表达。培养上清液中可溶性HAI-1的表达也显示同样的结果。雄激素影响部分前列腺细胞系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.