Metzner B, Hofmann C, Heinemann C, Zimpfer U, Schraufstätter I, Schöpf E, Norgauer J
Clinic of Dermatology, Divisions of Experimental and Clinical Dermatology, University of Freiburg, Freiburg, Germany.
Oncol Rep. 1999 Nov-Dec;6(6):1405-10. doi: 10.3892/or.6.6.1405.
The CXC-chemokines Groalpha and interleukin-8 (IL-8) are well characterized growth factors for melanoma cells. Here the constitutive expression of Groalpha, IL-8 and their receptors (CXCR1 and CXCR2) as well as their functional involvement in the proliferation response were analyzed in normal keratinocytes and epidermoid carcinoma cell lines A431 and KB. Flow cytometric measurements, ELISA and semi-quantitative RT-PCR revealed low constitutive protein secretion and mRNA expression of both CXC-chemokines as well as CXCR1 and 2 in normal keratinocytes, whereas significant higher levels of CXC-chemokines and CXCR2 were deteced in epidermoid carcinoma cells. Proliferation of epidermoid carcinoma cells could be induced by CXC-chemokines and constitutive proliferation could be inhibited by neutralizing antibodies against CXC-chemokines and CXCR2. These studies indicate that constitutive Groalpha, IL-8 and CXCR2 protein expression enable an autocrine growth mechanism in epidermoid carcinoma cells.
CXC趋化因子Groα和白细胞介素-8(IL-8)是已得到充分表征的黑色素瘤细胞生长因子。在此,对正常角质形成细胞以及表皮样癌细胞系A431和KB中Groα、IL-8及其受体(CXCR1和CXCR2)的组成性表达及其在增殖反应中的功能参与情况进行了分析。流式细胞术测量、酶联免疫吸附测定(ELISA)和半定量逆转录聚合酶链反应(RT-PCR)显示,正常角质形成细胞中这两种CXC趋化因子以及CXCR1和2的组成性蛋白分泌和mRNA表达水平较低,而在表皮样癌细胞中检测到CXC趋化因子和CXCR2的水平显著更高。表皮样癌细胞的增殖可由CXC趋化因子诱导,而组成性增殖可被针对CXC趋化因子和CXCR2的中和抗体抑制。这些研究表明,组成性的Groα、IL-8和CXCR2蛋白表达在表皮样癌细胞中促成了一种自分泌生长机制。