Goodwin G, Baylin S B
Cancer Res. 1982 Apr;42(4):1361-7.
After 16 months, an established line of human small cell lung cancer (OH-1) underwent a subtle morphological change which was associated with a virtually complete loss of neuroendocrine differentiation as judged by electron microscopy studies and a 12-fold loss in L-dopa decarboxylase activity. In nude (athymic) mouse heterotransplants, the histology of the early-passage cells (oat or lymphocyte-like) differed only slightly from the late-passage cells (intermediate or polygonal type); cytology studies showed no diagnostic differences between the passages. However, the early-passage endocrine-like cells showed up to 100-fold less cell survival after irradiation than the late-passage cells. Thus, subtle changes in the morphology of OH-1 cells are accompanied by a profound loss of neuroendocrine differentiation and the emergence of radiation resistance. These changes could have important parallelisms for behavior of small-cell lung carcinoma in humans. The cell culture model described may be useful in investigating the interrelationships occurring between endocrine and nonendocrine cells in the spectrum of human lung cancer. The findings emphasize that neuroendocrine-related ultrastructure and biochemistry may help define important cell populations in lung cancer with respect to therapeutic sensitivity.
16个月后,一株已建立的人小细胞肺癌细胞系(OH-1)发生了细微的形态学变化,通过电子显微镜研究判断,这种变化与神经内分泌分化几乎完全丧失以及L-多巴脱羧酶活性下降12倍有关。在裸(无胸腺)小鼠异种移植中,早期传代细胞(燕麦或淋巴细胞样)的组织学与晚期传代细胞(中间或多边形类型)仅略有不同;细胞学研究表明各传代之间没有诊断差异。然而,早期传代的类内分泌细胞在照射后的细胞存活率比晚期传代细胞低达100倍。因此,OH-1细胞形态的细微变化伴随着神经内分泌分化的严重丧失和辐射抗性的出现。这些变化可能与人类小细胞肺癌的行为具有重要的相似性。所描述的细胞培养模型可能有助于研究人类肺癌谱系中内分泌细胞和非内分泌细胞之间的相互关系。这些发现强调,神经内分泌相关的超微结构和生物化学可能有助于根据治疗敏感性来定义肺癌中的重要细胞群体。