Laminin and type VII collagen distribution in different types of human lung carcinoma: correlation with expression of keratins 14, 16, 17 and 18

Abstract

The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.

Clinical significance of serum laminin levels in patients with lung cancer

“…Using monoclonal antibodies, laminin expression as a basement membrane component and keratin intermediate filament protein in normal human bronchial epithelium and 56 lung carcinomas was assessed by Wetzels et al (1). In normal lung tissues, laminin was located around the alveoli and beneath the epithelial basal cell layer in bronchi and bronchioles.…”

“…Therefore, the interaction of the lung cancer cells with the extracellular matrix (ECM) in the way of cell adhesion, migration, proliferation and metastasis has been observed. Laminin, one of the major structural components of the basement membrane, is a strong promoter of cell adhesion, migration, differentiation and proliferation by means of integrins and other cell surface receptors (1)(2)(3)(4). Increased laminin expression was also detected in lung cancer cell lines with increased lung cancer cell proliferation and metastatic potential (1)(2)(3)(4).…”

“…Although there are increasing data regarding the role of laminin in various malignancies, only a few studies of laminin expression in lung cancer have been reported (1)(2)(3). However, the current available findings have been provided from preclinical tissue or cell-based trials.…”

Genetic Predisposition to Cutaneous Squamous Cell Carcinoma

“…Basement membrane of most tumors were devoid of type VII collagen expression, although some occasional staining is observed at sites containing laminin-332 (Nagle et al, 1994) Prostate carcinoma Loss of type VII collagen expression (Bonkhoff, 1998) Prostate carcinoma Early stromal invasion is associated with the loss of both hemidesmosomal proteins and type VII collagen but invasive tumor cells then go on to produce basement membrane-like matrices (Wetzels et al, 1992a) Lung Carcinoma…”

“…Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Conversely, down-regulation of the protein and/or mRNA is observed in cSCC (Dumas et al, 1999), melanoma tumours (Kirkham et al, 1989) and cell lines (Bechetoille et al, 2000), lung SCCs (Wetzels et al, 1992a), BCCs (Jones et al, 1989;Yasaka et al, 1994;Dumas et al, 1999), gastric carcinoma (Tani et al, 1996) and prostate carcinoma (Nagle et al, 1994;Bonkhoff, 1998). In prostate carcinogenesis, evidence points to the loss of type VII collagen as an early event which leads to dysplasia, (Bonkhoff, 1998).…”