Buckels Ashiya, Zhang Yue, Jiang Jing, Athar Mohammad, Afaq Farrukh, Shevde-Samant Lalita, Frank Stuart J
Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Biochem Biophys Rep. 2019 Dec 18;21:100716. doi: 10.1016/j.bbrep.2019.100716. eCollection 2020 Mar.
Melanoma is the most aggressive skin cancer. Its aggressiveness is most commonly attributed to ERK pathway mutations leading to constitutive signaling. Though initial tumor regression results from targeting this pathway, resistance often emerges. Interestingly, interrogation of the NCI-60 database indicates high growth hormone receptor (GHR) expression in melanoma cell lines. To further characterize melanoma, we tested responsiveness to human growth hormone (GH). GH treatment resulted in GHR signaling and increased invasion and migration, which was inhibited by a GHR monoclonal antibody (mAb) antagonist in WM35, SK-MEL 5, SK-MEL 28 and SK-MEL 119 cell lines. We also detected GH in the conditioned medium (CM) of human melanoma cell lines. GHR, JAK2 and STAT5 were basally phosphorylated in these cell lines, consistent with autocrine/paracrine GH production. Together, our results suggest that melanomas are enriched in GHR and produce GH that acts in an autocrine/paracrine manner. We suggest that GHR may constitute a therapeutic target in melanoma.
黑色素瘤是最具侵袭性的皮肤癌。其侵袭性最常见的原因是ERK通路突变导致组成性信号传导。尽管最初肿瘤消退是由于靶向该通路，但耐药性往往会出现。有趣的是，对NCI - 60数据库的研究表明黑色素瘤细胞系中生长激素受体（GHR）表达较高。为了进一步表征黑色素瘤，我们测试了其对人生长激素（GH）的反应性。GH处理导致GHR信号传导以及侵袭和迁移增加，在WM35、SK - MEL 5、SK - MEL 28和SK - MEL 119细胞系中，GHR单克隆抗体（mAb）拮抗剂可抑制这种增加。我们还在人黑色素瘤细胞系的条件培养基（CM）中检测到了GH。在这些细胞系中，GHR、JAK2和STAT5基础上被磷酸化，这与自分泌/旁分泌GH的产生一致。总之，我们的结果表明黑色素瘤中GHR丰富，并产生以自分泌/旁分泌方式起作用的GH。我们认为GHR可能构成黑色素瘤的一个治疗靶点。
