Modified basement membrane composition during bronchopulmonary tumor progression

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 (alpha 1, alpha 3 and alpha 5), Type VII collagen, and laminin 5 at different stages of bronchopulmonary cancers. In normal tissues, alpha 1(IV) chain was detected in all BMs (bronchial, vascular, alveolar, and glandular), alpha 5(IV) chain was present only in vascular BM, and laminin 5 and Type VII collagen were co-localized in bronchial and glandular BMs, whereas alpha 3(IV) immunolabeling was totally absent from normal bronchi. In well-differentiated carcinomas, alpha 3(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. alpha 1(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, alpha 3(IV) chain and Type VII collagen were not found, whereas laminin 5 and alpha 1(IV) chain persisted. The most important modifications in BM composition during tumor progression therefore appear to be the appearance of the alpha 3(IV) chain in well-differentiated carcinomas and its subsequent disappearance in poorly differentiated carcinomas, together with the loss of type VII collagen. alpha 5(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.