Ten Have-Opbroek A A, Benfield J R, van Krieken J H, Dijkman J H
Department of Pneumology, Leiden University, Netherlands.
Histol Histopathol. 1997 Apr;12(2):319-36.
Studies in a canine bronchogenic carcinoma model indicate that alveolar type II cells may differentiate from carcinogen-exposed epithelium of larger bronchi and generate adenocarcinomas with bronchioloalveolar and other growth patterns. In this study, we investigated whether type II cells are one of the major proliferating cells (= stem cells) in the genesis of two major subsets of bronchogenic carcinoma in humans. Adenocarcinomas (17 bronchioloalveolar; 3 papillary; and 10 other) and squamous cell carcinomas (n = 27) as well as (pre)neoplastic lesions in adjacent bronchi and bronchioles were examined for the presence of type II cell markers and cellular proliferation markers (PCNA; Ki-67) using light and electron microscopy and immunohistochemistry. Distinctive features of type II cells, which do not depend upon the degree of cell maturity, are the approximately cuboid shape, large and roundish nucleus, cytoplasmic staining for surfactant protein A (SP-A), and presence of multilamellar bodies or their precursory forms. Cells with this phenotype were found in early progressive (i.e., dysplastic, in situ, microinvasive) lesions in conducting airways and in all the carcinomas investigated, although with a much greater abundance among glandular lesions compared to squamous lesions. The most consistent sites of type II cells were the basal and adjacent epithelial layers. Nuclear PCNA (Ki-67) expression usually predominated in the same region. None of the lesions displayed specific Clara cell features. Our findings strongly suggest that the type II cell is a pluripotential stem cell in human lung carcinogenesis. Based on our findings in humans and dogs, we postulate that type II tumor stem cells may originate from one of two sources: (1) normal bronchial epithelium (by an oncofetal mechanism of differentiation); and (2) normal alveolar type II cells.
对犬支气管源性癌模型的研究表明，Ⅱ型肺泡细胞可能由暴露于致癌物的较大支气管上皮细胞分化而来，并产生具有细支气管肺泡及其他生长模式的腺癌。在本研究中，我们调查了Ⅱ型细胞是否是人类支气管源性癌两个主要亚群发生过程中的主要增殖细胞（即干细胞）之一。我们利用光学显微镜、电子显微镜及免疫组织化学方法，检测了腺癌（17例细支气管肺泡癌、3例乳头状癌和10例其他类型）、鳞状细胞癌（n = 27）以及相邻支气管和细支气管的（癌前）病变中Ⅱ型细胞标志物和细胞增殖标志物（增殖细胞核抗原；Ki-67）的存在情况。Ⅱ型细胞的显著特征不依赖于细胞成熟程度，包括近似立方形的形状、大而圆形的细胞核、表面活性蛋白A（SP-A）的胞质染色以及存在板层小体或其前体形式。具有这种表型的细胞在传导气道的早期进展性（即发育异常、原位、微浸润）病变以及所有研究的癌组织中均有发现，尽管在腺性病变中的丰度远高于鳞状病变。Ⅱ型细胞最常见的部位是基底上皮层和相邻上皮层。增殖细胞核抗原（Ki-67）的核表达通常在同一区域占主导。所有病变均未显示出特异性的克拉拉细胞特征。我们的研究结果强烈表明，Ⅱ型细胞是人类肺癌发生过程中的多能干细胞。基于我们在人类和犬类中的研究结果，我们推测Ⅱ型肿瘤干细胞可能起源于以下两种来源之一：（1）正常支气管上皮（通过肿瘤胎儿分化机制）；（2）正常Ⅱ型肺泡细胞。
