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 α3 and α5 in 40 adeno‐carcinomas and 8 squamous cell carcinomas. The α5 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 α3 chain were more prominent than for α5 chain. Laminin α3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from α5 chain. Non‐small cell lung cancers with reduced α5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin α3 and α5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express a3 chain and expression of α5 chain was reduced in three. Quantitative RT‐PCR analysis also demonstrated expression of laminin α3 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.