Ghrelin and cortistatin in lung cancer:: Expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line
Ghrelin and cortistatin in lung cancer:: Expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line
复制标题
DOI：
10.1007/bf03347371
复制
发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Papotti, M.
中科院分区：
文献类型：
--
作者：
Cassoni, P.;Allia, E.;Papotti, M.
Ghrelin是一种天然的GH分泌因子（GHS）酰化肽，而皮质抑素（CST）是一种天然的srif样颗粒，它们干扰不同癌症的肿瘤生长。我们对41例肺癌和H345小细胞肺癌（SCLC）细胞系进行了RT-PCR检测，以研究ghrelin和CST及其相关受体的存在，包括1a型GHS受体（GHS- r1a）、所有srif受体亚型（sst 1-5）和MRGX2。此外，我们还研究了ghrelin和CST肽在肿瘤和H345细胞中的存在。Ghrelin和CST mRNA存在于大多数测试的肿瘤中，但Ghrelin和CST蛋白仅在神经内分泌表型的肿瘤中被发现。所有受体mRNA均呈异质表达，与ghrelin（或CST）及其受体分布无关。除GHS-R1 a外，所有转录本均在H345细胞中表达。然而，胃饥饿素和去酰基胃饥饿素在体外对H345细胞增殖和凋亡增加有剂量依赖性的抑制作用。相反，CST和SRIF都不影响H345细胞的生长，尽管它们的特异性受体存在。ghrelin的抗增殖和促凋亡作用与H345细胞的结合实验一致，其中酰化或去酰化的ghrelin识别一个共同的结合位点。总之，本研究表明：a) ghrelin和CST mrna在肺癌中表达，尽管一些神经内分泌肿瘤含有可检测到的肽量；b) GHSR-1a mRNA仅存在于神经内分泌肿瘤中，而MRGX2 mRNA（不包括肽）在所有组织学类型中均有表达；c)尽管GHS-R1a不存在，但两种ghrelin形式均可直接抑制H345细胞增殖并促进细胞凋亡，而CST及其受体不干扰细胞生长。
Ghrelin, a natural GH secretagog (GHS) acylated peptide, and cortistatin (CST), a natural SRIF-like pepticle, interfere with neoplastic growth in different cancers. We tested forty-one lung carcinomas and the H345 small cell lung carcinoma (SCLC) cell line by RT-PCR to investigate the presence of ghrelin and CST and related receptors, including type 1 a GHS receptor (GHS-R1a), all SRIF-receptor subtypes (sst 1-5) and MRGX2. Moreover, the presence of ghrelin and CST peptides was studied in both tumors and H345 cells. Ghrelin and CST mRNA were present in the majority of tested tumors, but ghrelin and CST proteins were revealed only in tumors with a neuroendocrine phenotype. All the receptors mRNA had a heterogeneous expression without correlation between ghrelin (or CST) and their receptor distribution. All the transcripts, but not GHS-R1 a, were expressed in H345 cells. However, ghrelin and desacyl ghrelin induced in vitro a dose-dependent inhibition on the H345 cell proliferation and increased apoptosis. Conversely, neither CST nor SRIF affected H345 cell growth, despite the presence of their specific receptors. The anti-proliferative and the pro-apoptotic effects of ghrelin were consistent with binding experiments on H345 cell, where either acylated or des-acylated ghrelin recognized a common binding site. In conclusion, the present study indicates that: a) ghrelin and CST mRNAs are expressed in lung cancers, although some neuroendocrine tumors contain detectable amounts of the peptides; b) GHSR-1a mRNA is present exclusively in neuroendocrine tumors, whereas MRGX2 mRNA (but not peptide) is expressed in all histological types; c) both ghrelin forms inhibit H345 cell proliferation, both directly and enhancing apoptosis, despite the absence of GHS-R1a, whereas CST and its receptors do not interfere with cell growth.