Angiopoietin-like protein 2 induces androgen-independent and malignant behavior in human prostate cancer cells.

Angiopoietin-like proteins (ANGPTLs), which comprise 7 members (ANGPTL1-ANGPTL7), structurally resemble angiopoietins. We investigated the roles of ANGPTLs in the acquisition of androgen independence and the malignant behavior of human prostate cancer cells. Expression of ANGPTL messenger RNA (mRNA) and proteins were ascertained using RT-qPCR and western blot analysis in human prostate cancer cell lines. Androgen-dependent LNCaP and androgen-independent LNCaP/AI cells, respectively, were cultured in fetal bovine and charcoal-stripped medium. Cell proliferation, androgen dependence, migration and invasion, respectively, were examined under the overexpression and knockdown of ANGPTL2 by transfection of ANGPTL2 cDNA and its small-interfering RNA (siRNA). The effects of exogenous ANGPTL2 and blocking of its receptor, integrin α5β1, were also investigated. Human prostate cancer cell lines predominantly expressed ANGPTL2 among the members. Interrupting ANGPTL2 expression with siRNA suppressed the proliferation, migration and invasion of LNCaP cells. LNCaP/AI cells showed a higher ANGPTL2 expression than that of LNCaP cells. Furthermore, siRNA led to apoptosis of LNCaP/AI cells. The ANGPTL2-overexpressing LNCaP cells markedly increased proliferation, epithelial-to-mesenchymal transition (EMT) and malignant behavior in androgen-deprived medium. The migration rates were increased depending on the concentration of ANGPTL2 recombinant protein and were inhibited by anti-integrin α5β1 antibodies. To the best of our knowledge, this is the first study to elucidate the expression of ANGPTL2 in human prostate cancer cells. ANGPTL2 may be important in the acquisition of androgen independency and tumor progression of prostate cancer in an autocrine and/or paracrine manner via the integrin α5β1 receptor. Targeting ANGPTL2 may therefore be an efficacious therapeutic modality for prostate cancer.

血管生成素样蛋白（ANGPTLs）包含7个成员（ANGPTL1 - ANGPTL7），在结构上与血管生成素相似。我们研究了ANGPTLs在人前列腺癌细胞获得雄激素非依赖性及恶性行为中的作用。通过实时定量聚合酶链反应（RT - qPCR）和蛋白质印迹分析确定人前列腺癌细胞系中ANGPTL信使核糖核酸（mRNA）和蛋白质的表达。雄激素依赖性的LNCaP细胞和雄激素非依赖性的LNCaP/AI细胞分别在胎牛血清和活性炭处理的培养基中培养。通过转染ANGPTL2互补脱氧核糖核酸（cDNA）及其小干扰核糖核酸（siRNA），在ANGPTL2过表达和敲低的情况下，分别检测细胞增殖、雄激素依赖性、迁移和侵袭。还研究了外源性ANGPTL2及其受体整合素α5β1阻断的影响。在这些成员中，人前列腺癌细胞系主要表达ANGPTL2。用siRNA干扰ANGPTL2表达可抑制LNCaP细胞的增殖、迁移和侵袭。LNCaP/AI细胞比LNCaP细胞显示出更高的ANGPTL2表达。此外，siRNA可导致LNCaP/AI细胞凋亡。在雄激素剥夺的培养基中，ANGPTL2过表达的LNCaP细胞显著增加增殖、上皮 - 间质转化（EMT）和恶性行为。迁移率随ANGPTL2重组蛋白浓度增加而增加，并被抗整合素α5β1抗体抑制。据我们所知，这是第一项阐明ANGPTL2在人前列腺癌细胞中表达的研究。ANGPTL2可能通过整合素α5β1受体以自分泌和/或旁分泌方式在前列腺癌获得雄激素非依赖性和肿瘤进展中起重要作用。因此，靶向ANGPTL2可能是一种治疗前列腺癌的有效方法。