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Interleukin-13 receptor α2 is a novel marker and potential therapeutic target for human melanoma

机译:白细胞介素13受体α2是人类黑素瘤的新标志物和潜在治疗靶标

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摘要

Malignant melanoma is one of the untreatable cancers in which conventional therapeutic strategies, including chemotherapy, are hardly effective. Therefore, identification of novel therapeutic targets involved in melanoma progression is urgently needed for developing effective therapeutic methods. Overexpression of interleukin-13 receptor α2 (IL13Rα2) is observed in several cancer types including glioma and pancreatic cancer. Although IL13Rα2 is implicated in the progression of various types of cancer, its expression and roles in the malignant melanoma have not yet been elucidated. In the present study, we showed that IL13Rα2 was expressed in approximately 7.5% melanoma patients. While IL13Rα2 expression in human melanoma cells decreased their proliferation in vitro, it promoted in vivo tumour growth and angiogenesis in melanoma xenograft mouse model. We also found that the expression of amphiregulin, a member of the epidermal growth factor (EGF) family, was correlated with IL13Rα2 expression in cultured melanoma cells, xenograft tumour tissues and melanoma clinical samples. Furthermore, expression of amphiregulin promoted tumour growth, implicating causal relationship between the expression of IL13Rα2 and amphiregulin. These results suggest that IL13Rα2 enhances tumorigenicity by inducing angiogenesis in malignant melanoma, and serves as a potential therapeutic target of malignant melanoma.
机译:恶性黑色素瘤是不可治愈的癌症之一,其中包括化学疗法在内的常规治疗策略几乎无效。因此,迫切需要鉴定涉及黑素瘤进展的新治疗靶标以开发有效的治疗方法。在包括胶质瘤和胰腺癌在内的几种癌症类型中观察到白介素13受体α2(IL13Rα2)的过表达。尽管IL13Rα2与各种类型的癌症的发展有关,但尚未阐明其在恶性黑色素瘤中的表达和作用。在本研究中,我们显示IL13Rα2在大约7.5%的黑色素瘤患者中表达。虽然人黑素瘤细胞中IL13Rα2的表达降低了其体外增殖,但它促进了黑素瘤异种移植小鼠模型的体内肿瘤生长和血管生成。我们还发现,表皮生长因子(EGF)家族成员双调蛋白的表达与培养的黑素瘤细胞,异种移植肿瘤组织和黑素瘤临床样品中的IL13Rα2表达相关。此外,双调蛋白的表达促进肿瘤生长,暗示IL13Rα2的表达与双调蛋白之间的因果关系。这些结果表明,IL13Rα2通过诱导恶性黑色素瘤中的血管生成来增强致瘤性,并且作为恶性黑色素瘤的潜在治疗靶标。

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