Moody T W, Cuttitta F
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington, D.C. 20037.
Life Sci. 1993;52(14):1161-73. doi: 10.1016/0024-3205(93)90098-n.
In the past decade, over 1000 continuous human cell lines have been established from lung cancer biopsy specimens. Numerous growth factors and receptors have been identified in the small cell lung cancer (SCLC) cell lines. SCLC is a neuroendocrine tumor which contains numerous peptides, including bombesin/gastrin releasing peptide (BN/GRP), and receptors. High levels of GRP mRNA and immunoreactivity are present in SCLC cells. The secretion rate of GRP from SCLC cells is increased by vasoactive intestinal peptide (VIP), which elevates the intracellular cAMP. GRP binds to cell surface receptors, elevates cytosolic calcium and stimulates the growth of SCLC cells. Additional SCLC growth factors include insulin-like growth factor I (IGF-I) and transferrin. IGF-I mRNA and protein is present in SCLC. IGF-I binds with high affinity to SCLC cells and stimulates tyrosine kinase activity and growth. Transferrin is also present in SCLC cells. Transferrin binds with high affinity to SCLC cells and stimulates iron transport and growth. Synthetic peptide antagonists and monoclonal antibodies have been identified which disrupt autocrine growth pathways and inhibit SCLC growth.
在过去十年中，已从肺癌活检标本中建立了1000多种连续的人类细胞系。在小细胞肺癌（SCLC）细胞系中已鉴定出许多生长因子和受体。SCLC是一种神经内分泌肿瘤，含有许多肽，包括蛙皮素/胃泌素释放肽（BN/GRP）和受体。SCLC细胞中存在高水平的GRP mRNA和免疫反应性。血管活性肠肽（VIP）可增加SCLC细胞中GRP的分泌率，VIP可提高细胞内cAMP水平。GRP与细胞表面受体结合，升高胞质钙并刺激SCLC细胞生长。其他SCLC生长因子包括胰岛素样生长因子I（IGF-I）和转铁蛋白。IGF-I mRNA和蛋白存在于SCLC中。IGF-I与SCLC细胞高亲和力结合并刺激酪氨酸激酶活性和生长。转铁蛋白也存在于SCLC细胞中。转铁蛋白与SCLC细胞高亲和力结合并刺激铁转运和生长。已鉴定出可破坏自分泌生长途径并抑制SCLC生长的合成肽拮抗剂和单克隆抗体。
