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首页> 外文期刊>Oncogene >PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer
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PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer

机译：PTRF / cavin-1中和前列腺癌中的非小窝小窝蛋白-1微结构域

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Caveolin-1 has a complex role in prostate cancer and has been suggested to be a potential biomarker and therapeutic target. As mature caveolin-1 resides in caveolae, invaginated lipid raft domains at the plasma membrane, caveolae have been suggested as a tumor-promoting signaling platform in prostate cancer. However, caveola formation requires both caveolin-1 and cavin-1 (also known as PTRF; polymerase I and transcript release factor). Here, we examined the expression of cavin-1 in prostate epithelia and stroma using tissue microarray including normal, non-malignant and malignant prostate tissues. We found that caveolin-1 was induced without the presence of cavin-1 in advanced prostate carcinoma, an expression pattern mirrored in the PC-3 cell line. In contrast, normal prostate epithelia expressed neither caveolin-1 nor cavin-1, while prostate stroma highly expressed both caveolin-1 and cavin-1. Utilizing PC-3 cells as a suitable model for caveolin-1-positive advanced prostate cancer, we found that cavin-1 expression in PC-3 cells inhibits anchorage-independent growth, and reduces in vivo tumor growth and metastasis in an orthotopic prostate cancer xenograft mouse model. The expression of 伪-smooth muscle actin in stroma along with interleukin-6 (IL-6) in cancer cells was also decreased in tumors of mice bearing PC-3-cavin-1 tumor cells. To determine whether cavin-1 acts by neutralizing caveolin-1, we expressed cavin-1 in caveolin-1-negative prostate cancer LNCaP and 22Rv1 cells. Caveolin-1 but not cavin-1 expression increased anchorage-independent growth in LNCaP and 22Rv1 cells. Cavin-1 co-expression reversed caveolin-1 effects in caveolin-1-positive LNCaP cells. Taken together, these results suggest that caveolin-1 in advanced prostate cancer is present outside of caveolae, because of the lack of cavin-1 expression. Cavin-1 expression attenuates the effects of non-caveolar caveolin-1 microdomains partly via reduced IL-6 microenvironmental function. With circulating caveolin-1 as a potential biomarker for advanced prostate cancer, identification of the molecular pathways affected by cavin-1 could provide novel therapeutic targets.
机译：Caveolin-1在前列腺癌中具有复杂的作用，并被认为是潜在的生物标志物和治疗靶标。由于成熟的caveolin-1驻留在caveolae中，质膜上的脂质筏域已被入侵，因此caveolae被认为是前列腺癌中促进肿瘤的信号平台。但是，小窝形成需要小窝-1和cavin-1（也称为PTRF;聚合酶I和转录释放因子）。在这里，我们使用包括正常，非恶性和恶性前列腺组织在内的组织芯片检查了cavin-1在前列腺上皮和间质中的表达。我们发现在晚期前列腺癌中不存在cavin-1的情况下诱导了caveolin-1，这种表达模式在PC-3细胞系中得到了反映。相反，正常的前列腺上皮既不表达caveolin-1也不表达cavin-1，而前列腺基质高度表达cavolin-1和cavin-1。利用PC-3细胞作为卡夫林1阳性晚期前列腺癌的合适模型，我们发现PC-3细胞中cavin-1的表达抑制了锚定非依赖性生长，并降低了体内肿瘤的生长和转移。原位前列腺癌异种移植小鼠模型。在带有PC-3-cavin-1肿瘤细胞的小鼠的肿瘤中，癌细胞中白细胞中α-平滑肌肌动蛋白的表达也与白细胞介素6（IL-6）降低。为了确定cavin-1是否通过中和caveolin-1起作用，我们在caveolin-1阴性前列腺癌LNCaP和22Rv1细胞中表达了cavin-1。在LNCaP和22Rv1细胞中，Caveolin-1表达而非cavin-1表达增加了锚定非依赖性生长。 Cavin-1共表达可逆转小窝蛋白1阳性LNCaP细胞中小窝蛋白1的作用。两者合计，这些结果表明，由于缺乏cavin-1表达，晚期前列腺癌中的caveolin-1存在于caveolae之外。 Cavin-1表达部分通过减少IL-6微环境功能来减弱非小窝小窝蛋白1微结构域的作用。随着循环caveolin-1作为晚期前列腺癌的潜在生物标志物，cavin-1影响的分子途径的鉴定可以提供新的治疗靶点。

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