Ciaramella Vincenza, Della Corte Carminia Maria, Di Mauro Concetta, Tomassi Stefano, Di Maro Salvatore, Troiani Teresa, Martinelli Erika, Bianco Roberto, Cosconati Sandro, Pierantoni Riccardo, Meccariello Rosaria, Chianese Rosanna, Ciardiello Fortunato, Morgillo Floriana
Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi", Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.
Oncologia Medica, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", Naples, Italy.
Oncotarget. 2018 Apr 10;9(27):19273-19282. doi: 10.18632/oncotarget.25018.
Kisspeptin signaling, its receptors GPR54, could be an essential players in the inhibition of mesothelioma progression, invasion and metastasis formation. The loss of KiSS1 by tumor cells has been associated with a metastatic phenotype but the mechanistic insights of this process are still unknown.
The blockade of the metastatic process at early stage is a hot topic in cancer research. We studied the role of KiSS1 on proliferation, invasiveness, migration abilities of mesothelioma cell lines focusing on the effect on epithelial-to-mesenchymal transition (EMT).
Treatment with the KiSS1 peptide or with a synthesis peptide with longer half-life, the FTM080, significantly inhibited cell proliferation, migration and invasion of mesothelioma cell lines; the same treatment reduced the activity of MMP-2 and MMP-9 determining consequently a marked reduction in the invasiveness of primary tumors and metastases. Thespecificexpression of EMT markers, as E-caderin, Vimentin, Slug and Snail, suggested the inhibition of EMT after treatment with KiSS1 as well as the preservation of epithelial components.
Our results support anti-proliferative effect of KiSS1 in cancer cells and suggest that targeting the KiSS1/GPR54 system may represent a novel therapeutic approach for mesothelioma.
亲吻素信号传导及其受体GPR54可能是抑制间皮瘤进展、侵袭和转移形成的关键因素。肿瘤细胞中KiSS1的缺失与转移表型相关，但该过程的机制仍不清楚。
在癌症研究中，早期阻断转移过程是一个热门话题。我们研究了KiSS1对间皮瘤细胞系增殖、侵袭和迁移能力的作用，重点关注其对上皮-间质转化（EMT）的影响。
用KiSS1肽或半衰期更长的合成肽FTM080处理，可显著抑制间皮瘤细胞系的细胞增殖、迁移和侵袭；相同处理降低了MMP-2和MMP-9的活性，从而显著降低了原发性肿瘤和转移灶的侵袭性。EMT标志物如E-钙黏蛋白、波形蛋白、锌指蛋白和蜗牛蛋白的特异性表达表明，用KiSS1处理后EMT受到抑制，上皮成分得以保留。
我们的结果支持KiSS1在癌细胞中的抗增殖作用，并表明靶向KiSS1/GPR54系统可能是间皮瘤的一种新的治疗方法。
