Yang Y, Mou Lj, Liu N, Tsao M S
Ontario Cancer Institute and Toronto Hospital-Princess Margaret Hospital, Toronto, Ontario, Canada.
Am J Respir Cell Mol Biol. 1999 Aug;21(2):216-22. doi: 10.1165/ajrcmb.21.2.3667.
Autotaxin (ATX) is one of the newly discovered autocrine motility-stimulating factors with peptide sequences identical to those of the brain-type phosphodiesterase I (PD-Ialpha). Although ATX/PD-Ialpha is believed to play a role in tumor progression, its expression in various human cancers has not been extensively studied. We have studied the expression of ATX messenger RNA (mRNA) in normal human bronchial epithelial cell (HBEC) and non-small-cell lung cancer (NSCLC) cell lines, and in primary NSCLC with their corresponding normal lung tissues, using reverse transcription-polymerase chain reaction, Northern blot analysis, and in situ hybridization. ATX mRNA was commonly expressed in these cell lines and tissues. The predominantly expressed mRNA species corresponded to the ATX complementary DNA isolated from a human teratocarcinoma cell line. Overexpression of ATX mRNA was detected in seven of 12 (58%) tumor cell lines; however, there was no correlation between the levels of expression of ATX mRNA and the spontaneous motility of these cells. In situ hybridization localized ATX mRNA expression to the basal cells of normal bronchial epithelium, stromal B lymphocytes, and tumor cells. An overexpression of ATX mRNA as compared with its expression in normal bronchial epithelium was mainly found in poorly differentiated carcinomas. Our findings suggest that ATX may have roles additional to its motility-stimulating function in undifferentiated NSCLC.
自分泌运动因子(ATX)是新发现的自分泌运动刺激因子之一,其肽序列与脑型磷酸二酯酶I(PD-Iα)相同。尽管ATX/PD-Iα被认为在肿瘤进展中起作用,但其在各种人类癌症中的表达尚未得到广泛研究。我们使用逆转录-聚合酶链反应、Northern印迹分析和原位杂交技术,研究了自分泌运动因子信使核糖核酸(mRNA)在正常人支气管上皮细胞(HBEC)、非小细胞肺癌(NSCLC)细胞系以及原发性NSCLC及其相应正常肺组织中的表达情况。ATX mRNA在这些细胞系和组织中普遍表达。主要表达的mRNA种类与从人畸胎瘤细胞系中分离出的ATX互补DNA相对应。在12个肿瘤细胞系中的7个(58%)检测到ATX mRNA的过表达;然而,ATX mRNA的表达水平与这些细胞的自发运动性之间没有相关性。原位杂交将ATX mRNA的表达定位在正常支气管上皮的基底细胞、基质B淋巴细胞和肿瘤细胞中。与正常支气管上皮中的表达相比,ATX mRNA的过表达主要见于低分化癌。我们的研究结果表明,在未分化的NSCLC中,ATX可能除了具有其运动刺激功能外还有其他作用。