Modified basement membrane composition during bronchopulmonary tumor progression

During tumor progression, the extracellular matrix (ECM) and particularly t he basement membrane (BM) appear to be dynamic structures that are not only degraded but also deposited around tumor clusters. In this study we examin ed by immunohistochemistry the localization of three chains of Type IV coll agen (alpha 1, alpha 3 and alpha 5), Type VII collagen, and laminin 5 at di fferent 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 Typ e VII collagen were co-localized in bronchial and glandular BMs, whereas al pha 3(IV) immunolabeling was totally absent from normal bronchi. In well-di fferentiated carcinomas, alpha 3(IV) chain staining was found in some neosy nthetized BMs interfacing the tumor cell and the stromal compartment, contr asting with the total absence of labeling in normal tissues. alpha 1(IV) ch ain showed strong reactivity in all BM. Laminin 5 and Type VII collagen wer e also detected in neosynthetized BM. In poorly differentiated invasive can cers, alpha 3(IV) chain and Type VII collagen were not found, whereas lamin in 5 and alpha 1(IV) chain persisted. The most important modifications in B M composition during tumor progression therefore appear to be the appearanc e of the alpha 3(IV) chain in well-differentiated carcinomas and its subseq uent disappearance in poorly differentiated carcinomas, together with the l oss of type VII collagen. alpha 5(IV) chain distribution was restricted in vascular BM of well- and poorly differentiated carcinomas. These results sh ow that the composition of BM is modified during the progression of broncho pulmonary tumor, emphasizing that the BM represents a dynamic element in tu mor progression and has an important role in tumor cell invasiveness.