Reduced expression of laminin α3 and α5 chains in non-small cell lung cancers

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 alpha3 and alpha5 in 40 adenocarcinomas and 8 squamous cell carcinomas. The alpha5 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 alpha3 chain were more prominent than for alpha5 chain. Laminin alpha3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from alpha5 chain. Non-small cell lung cancers with reduced alpha5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin alpha3 and alpha5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express alpha3 chain and expression of alpha5 chain was reduced in three, Quantitative RT-PCR analysis also demonstrated expression of laminin alpha3 chain in adenocarcinoma tissues to be significantly lower than in normal lung tissues, These results suggest that expression of laminin a 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.