The antitumor potential of Interleukin-27 in prostate cancer.
The antitumor potential of Interleukin-27 in prostate cancer.
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DOI：
10.18632/oncotarget.1425
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发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Airoldi I
中科院分区：
文献类型：
--
作者：
Di Carlo E;Sorrentino C;Zorzoli A;Di Meo S;Tupone MG;Ognio E;Mincione G;Airoldi I
由于人口老龄化，前列腺癌（PCa）在全世界范围内变得越来越重要。体弱的老年患者可能特别受益于非侵入性且耐受性良好的免疫治疗方法。临床前研究表明，免疫调节细胞因子 IL-27 可能在多种肿瘤类型中发挥抗肿瘤活性，且没有明显的毒性。因此，我们研究了 IL-27 是否可以作为人 (h) PCa 中的抗肿瘤剂，并分析其临床应用的基本原理。在体外，IL-27治疗通过下调促血管生成相关基因fms相关酪氨酸激酶（FLT）1、前列腺素G/H合酶1/环加氧酶-1（PTGS1/COX-1）和成纤维细胞生长因子受体（FGFR）3，显着抑制增殖并降低hPCa细胞的血管生成潜力。此外，IL-27上调抗血管生成相关基因，如CXCL10和TIMP金属肽酶抑制剂3（TIMP3）。在体内，IL-27 减少了与无胸腺裸鼠注射 PC3 或 DU145 细胞后发生的肿瘤缺血性坏死相关的增殖和血管化。在患者的前列腺组织中，IL-27R 在正常上皮细胞和低级别 PCa 中表达，并在高级别肿瘤和分期中缺失。然而，IL-27R 由浸润肿瘤和引流淋巴结的 CD11c+、CD4+ 和 CD8+ 白细胞表达。这些数据得出以下结论：i) IL-27 的抗 PCa 潜力可在分化良好、局部 IL-27R 阳性 PCa 患者中得到充分利用，因为在这种情况下，它可能作用于癌性上皮和肿瘤微环境； ii) 然而，缺乏 IL-27R 的患有高级别和分期肿瘤的 PCa 患者可能会受益于 IL-27 的免疫刺激特性。
Prostate cancer (PCa) is of increasing significance worldwide as a consequence of the population ageing. Fragile elderly patients may particularly benefit from noninvasive and well tolerable immunotherapeutic approaches. Preclinical studies have revealed that the immune-regulatory cytokine IL-27 may exert anti-tumor activities in a variety of tumor types without discernable toxicity. We, thus, investigated whether IL-27 may function as anti-tumor agent in human (h) PCa and analyzed the rationale for its clinical application. In vitro, IL-27 treatment significantly inhibited proliferation and reduced the angiogenic potential of hPCa cells by down-regulating the pro-angiogenesis-related genes fms-related tyrosine kinase (FLT)1, prostaglandin G/H synthase 1/cyclooxygenase-1 (PTGS1/COX-1) and fibroblast growth factor receptor (FGFR)3. In addition, IL-27 up-regulated the anti-angiogenesis-related genes such as CXCL10 and TIMP metallopeptidase inhibitor 3 (TIMP3). In vivo, IL-27 reduced proliferation and vascularization in association with ischemic necrosis of tumors developed after PC3 or DU145 cell injection in athymic nude mice. In patients' prostate tissues, IL-27R was expressed by normal epithelia and low grade PCa and lost by high tumor grade and stages. Nevertheless, IL-27R was expressed by CD11c+, CD4+ and CD8+ leukocytes infiltrating the tumor and draining lymph nodes. These data lead to the conclusion that i) IL-27's anti-PCa potential may be fully exploited in patients with well-differentiated, localized IL-27R positive PCa, since in this case it may act on both cancerous epithelia and the tumor microenvironment; ii) PCa patients bearing high grade and stage tumor that lack IL-27R may benefit, however, from IL-27's immune-stimulatory properties.
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影响因子：
4.4
作者：
Shimizu, Motomu;Shimamura, Mariko;Yoshimoto, Takayuki
通讯作者：
Yoshimoto, Takayuki
影响因子：
2.1
作者：
Ferrer, FA;Miller, LJ;Kreutzer, DL
通讯作者：
Kreutzer, DL
影响因子：
11.2
作者：
Hisada, M;Kamiya, S;Yoshimoto, T
通讯作者：
Yoshimoto, T
影响因子：
64.5
作者：
Lichtenberger, Beate M.;Tan, Poi Kiang;Sibilia, Maria
通讯作者：
Sibilia, Maria
影响因子：
82.9
作者：
Qi, JH;Ebrahem, Q;Anand-Apte, B
通讯作者：
Anand-Apte, B