Somatomedin-C/insulin-like growth factor-I is a mitogen for human small cell lung cancer.
Somatomedin-C/insulin-like growth factor-I is a mitogen for human small cell lung cancer.
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DOI：
10.1038/bjc.1988.16
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发表时间：
1988-01
影响因子：
8.8
通讯作者：
Millar, J L
中科院分区：
文献类型：
--
作者：
Macauly, V M;Teale, J D;Everard, M J;Joshi, G P;Smith, I E;Millar, J L
小细胞肺癌(SCLC)的快速增殖可能与自分泌生长因子的合成有关。Bombein(或其哺乳动物同源物胃泌素释放肽，GRP)在小细胞肺癌中可能具有自分泌功能(Cuttitta等人，1985；Carney等人，1987)，但不能被生长更快的变异小细胞肺癌株系合成(Carney等人，1985)。生长抑素-C(Sm-C)/胰岛素样生长因子-I(IGF-I)是一种由70个氨基酸组成的碱性多肽，分子量为7.6kD，由40-150kD的结合蛋白在血清中携带(Underwood等，1986a)。它主要来自肝脏，但也来自包括肺在内的肝外部位(D‘Ercole等人，1984)。作为自分泌生长因子的功能已经在几个细胞系统中被描述，包括培养的人成纤维细胞(Clemmons等人，1981)和乳腺癌(Huff等人，1986)。Minuto等人(1986)报道了原发肺肿瘤组织手术标本中Sm-C的高水平。所有10个样本都是腺癌或鳞癌；没有给出小细胞肺癌的结果，可能是因为这些患者很少来做手术。最近的两项研究报告了人类大细胞肺癌细胞系表达多种生长因子的基因，包括IGF-II而不是IGF-I(Betsholtz等人，1987)，以及在SCLC条件培养液中存在类似胰岛素的分子(Cutty ta等人，1987)。我们一直在研究经典SCLC条件培养液的高相对分子质量(>；10kD)浓缩，这种浓缩对经典和变异的SCLC细胞株都是有丝分裂的，尽管它耗尽了蛙皮素/GRP(Macaulay等人，1987)。该浓缩物被发现含有免疫活性Sm-C，促使对人类肺组织和细胞系进行了调查。
Rapid proliferation in small cell lung cancer (SCLC) may be mediated by synthesis of autocrine growth factors. Bombesin (or its mammalian homologue gastrin releasing peptide, GRP) may have autocrine function in SCLC (Cuttitta et al., 1985; Carney et al., 1987) but is not synthesised by the faster growing variant SCLC lines (Carney et al., 1985). Somatomedin-C (Sm-C)/insulin-like growth factor-I (IGF-I) is a basic peptide of 70 amino acids and MW 7.6 kD which is carried in serum by binding proteins of 40-150 kD (Underwood et al., 1986a). It derives mainly from the liver but also from extrahepatic sites including lung (D'Ercole et al., 1984). Function as an autocrine growth factor has been described in several cell systems, including cultured human fibroblasts (Clemmons et al., 1981) and breast carcinoma (Huff et al., 1986). Minuto et al (1986) reported high levels of Sm-C in operative specimens of primary lung tumour tissue. All 10 samples were adeno-or squamous carcinoma; no results were given for SCLC, presumably because these patients rarely come to surgery. Two more recent studies have reported expression by a human large cell lung cancer line of genes for multiple growth factors including IGF-II but not IGF-I (Betsholtz et al., 1987), and the presence of'insulin-like'molecules in SCLC conditioned medium (Cuttitta et al., 1987).We have been working with a high molecular weight (> 10 kD) concentrate of classic SCLC conditioned medium which is mitogenic to both classic and variant SCLC lines despite being depleted of bombesin/GRP (Macaulay et al., 1987). The concentrate was found to contain immunoreactive Sm-C, prompting a survey of human lung tissues and cell lines.