Reduced expression of laminin alpha 3 and alpha 5 chains in non-small cell lung cancers

Abstract

The basement membrane is considered to act as a barrier which hinders cancer cells from invading the surrounding stroma. In order to assess changes in essential components during neoplasia in the lung, we immunohistochemically studied distribution patterns of laminins alpha 3 and alpha 5 in 40 adenocarcinomas and 8 squamous cell carcinomas. The a 5 chain was generally preserved at the periphery, frequently disrupted in foci with alveolar collapse and absent in foci of fibroblastic proliferation within adenocarcinomas. Fragmentation and absence of laminin alpha 3 chain were more prominent than for alpha 5 chain. Laminin alpha 3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from alpha 5 chain. Non-small cell lung cancers with reduced alpha 5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin alpha 3 and alpha 5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express alpha 3 chain and expression of alpha 5 chain was reduced in three. Quantitative RT-PCR analysis also demonstrated expression of laminin alpha 3 chain in adenocarcinoma tissues to be significantly lower than in normal lung tissues. These results suggest that expression of laminin alpha chains is often reduced in lung cancer cells and this might contribute to basement membrane fragmentation and subsequent proliferation of stromal elements, as well as play some role in the process of cancer cell invasion.