Catusse C, Polette M, Coraux C, Burlet H, Birembaut P
INSERM U514, IFR 53, Unité de Biologie Cellulaire, Laboratoire Pol Bouin, CHU Maison Blanche, Reims, France.
J Histochem Cytochem. 2000 May;48(5):663-9. doi: 10.1177/002215540004800510.
During tumor progression, the extracellular matrix (ECM) and particularly the basement membrane (BM) appear to be dynamic structures that are not only degraded but also deposited around tumor clusters. In this study we examined by immunohistochemistry the localization of three chains of Type IV collagen (alpha1, alpha3 and alpha5), Type VII collagen, and laminin 5 at different stages of bronchopulmonary cancers. In normal tissues, alpha1(IV) chain was detected in all BMs (bronchial, vascular, alveolar, and glandular), alpha5(IV) chain was present only in vascular BM, and laminin 5 and Type VII collagen were co-localized in bronchial and glandular BMs, whereas alpha3(IV) immunolabeling was totally absent from normal bronchi. In well-differentiated carcinomas, alpha3(IV) chain staining was found in some neosynthetized BMs interfacing the tumor cell and the stromal compartment, contrasting with the total absence of labeling in normal tissues. alpha1(IV) chain showed strong reactivity in all BM. Laminin 5 and Type VII collagen were also detected in neosynthetized BM. In poorly differentiated invasive cancers, alpha3(IV) chain and Type VII collagen were not found, whereas laminin 5 and alpha1(IV) chain persisted. The most important modifications in BM composition during tumor progression therefore appear to be the appearance of the alpha3 (IV) chain in well-differentiated carcinomas and its subsequent disappearance in poorly differentiated carcinomas, together with the loss of type VII collagen. alpha5(IV) chain distribution was restricted in vascular BM of well- and poorly differentiated carcinomas. These results show that the composition of BM is modified during the progression of bronchopulmonary tumor, emphasizing that the BM represents a dynamic element in tumor progression and has an important role in tumor cell invasiveness.
在肿瘤进展过程中，细胞外基质（ECM）尤其是基底膜（BM）似乎是动态结构，不仅会被降解，还会在肿瘤簇周围沉积。在本研究中，我们通过免疫组织化学检查了IV型胶原的三条链（α1、α3和α5）、VII型胶原和层粘连蛋白5在支气管肺癌不同阶段的定位。在正常组织中，α1（IV）链在所有基底膜（支气管、血管、肺泡和腺泡）中均有检测到，α5（IV）链仅存在于血管基底膜中，层粘连蛋白5和VII型胶原共定位于支气管和腺泡基底膜，而正常支气管中完全没有α3（IV）免疫标记。在高分化癌中，在一些连接肿瘤细胞和基质成分的新合成基底膜中发现了α3（IV）链染色，这与正常组织中完全没有标记形成对比。α1（IV）链在所有基底膜中均显示出强反应性。在新合成的基底膜中也检测到了层粘连蛋白5和VII型胶原。在低分化浸润性癌中，未发现α3（IV）链和VII型胶原，而层粘连蛋白5和α1（IV）链持续存在。因此，在肿瘤进展过程中基底膜组成的最重要变化似乎是高分化癌中α3（IV）链的出现及其在低分化癌中的随后消失，以及VII型胶原的丧失。α5（IV）链分布在高分化和低分化癌的血管基底膜中受到限制。这些结果表明，在支气管肺肿瘤进展过程中基底膜的组成发生了改变，强调基底膜是肿瘤进展中的一个动态元素，并且在肿瘤细胞侵袭中起重要作用。
