Manda R, Kohno T, Niki T, Yamada T, Takenoshita S, Kuwano H, Yokota J
Biology, Pathology Divisions, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Tokyo, Chuo-ku, 104-0045, Japan.
Biochem Biophys Res Commun. 2000 Aug 28;275(2):440-5. doi: 10.1006/bbrc.2000.3331.
To identify genes differentially expressed between small cell lung carcinoma (SCLC) cells and non-SCLC cells, mRNA differential display was applied to 3 SCLC cell lines and 6 non-SCLC cell lines. The LAMB3 gene was identified as being expressed only in non-SCLC cells and not in SCLC cells. The LAMB3 gene encodes the laminin beta3 chain, which is a unique component of laminin-5. Laminin-5 is a heterotrimer protein consisting of the alpha3, beta3, and gamma2 chains, and another unique component of laminin-5 is the gamma2 chain encoded by the LAMC2 gene. RT-PCR analysis of the LAMB3 and LAMC2 genes in 45 lung cancer cell lines revealed that both the LAMB3 and LAMC2 genes were co-expressed in 21 of 32 non-SCLC cell lines (66%) but only in one of 13 SCLC cell lines (8%). Coexpression of the LAMB3 and LAMC2 genes was also observed in all 4 cases of primary non-SCLC cells examined but not in the corresponding non-cancerous lung cells. Since alpha6beta4 integrin, the specific laminin-5 binding receptor, is known to be expressed only in non-SCLC cells and not in SCLC cells, it was indicated that laminin-5 is a critical microenvironmental factor for the growth of non-SCLC cells but not of SCLC cells. The differences in the expression of integrins and laminins would be critical factors to distinguish SCLC and non-SCLC cells, and such differences might be associated with the unique biological properties of SCLC cells, including metastatic potential and drug sensitivity.
为了鉴定小细胞肺癌（SCLC）细胞和非小细胞肺癌（non-SCLC）细胞之间差异表达的基因，对3种SCLC细胞系和6种non-SCLC细胞系进行了mRNA差异显示分析。LAMB3基因被鉴定为仅在non-SCLC细胞中表达，而在SCLC细胞中不表达。LAMB3基因编码层粘连蛋白β3链，它是层粘连蛋白-5的独特组成成分。层粘连蛋白-5是一种由α3、β3和γ2链组成的异源三聚体蛋白，层粘连蛋白-5的另一个独特组成成分是由LAMC2基因编码的γ2链。对45种肺癌细胞系中的LAMB3和LAMC2基因进行RT-PCR分析发现，LAMB3和LAMC2基因在32种non-SCLC细胞系中的21种（66%）中共同表达，但在13种SCLC细胞系中仅在1种（8%）中共同表达。在所检测的所有4例原发性non-SCLC细胞中也观察到LAMB3和LAMC2基因的共同表达，但在相应的非癌性肺细胞中未观察到。由于已知特异性层粘连蛋白-5结合受体α6β4整合素仅在non-SCLC细胞中表达，而在SCLC细胞中不表达，这表明层粘连蛋白-5是non-SCLC细胞生长的关键微环境因子，而不是SCLC细胞生长的关键微环境因子。整合素和层粘连蛋白表达的差异可能是区分SCLC和non-SCLC细胞的关键因素，并且这种差异可能与SCLC细胞的独特生物学特性有关，包括转移潜能和药物敏感性。
