Variant expression of CD44 in preneoplastic lesions of the lung

Abstract

BACKGROUND Specific CD44 isoforms are cell surface adhesion molecules and have been shown to be associated with tumor progression and metastasis. In lung carcinoma, CD44 expression has been reported to be a feature of nonsmall cell lung carcinoma (NSCLC) but not small cell lung carcinoma. A specific variant, CD44v6, was shown to be expressed only in a subset of NSCLC, namely the squamous cell and bronchoalveolar carcinomas, suggesting that CD44 may play a role in lung carcinoma differentiation. METHODS To determine whether differential CD44 expression is an early event in the pathogenesis of lung carcinoma, the authors investigated the pattern of expression of the standard (CD44s) and variant (CD44v6) isoforms by immunohistochemistry in normal lung, nonneoplastic specimens, and bronchial biopsies of preneoplastic lesions. RESULTS In normal bronchial epithelium and all nonneoplastic cases, CD44s expression was limited to the basement membrane and adjacent lower strata of the epithelium, whereas CD44v6 was expressed within the basement membrane only. However, aberrant expression of both CD44s and CD44v6 was observed in all preneoplastic lesions examined. In cases of dysplasia, squamous metaplasia, goblet cell hyperplasia, and basal cell hyperplasia, all epithelial strata showed immunoreactivity for both isoforms, in contrast to normal epithelium, in which immunoreactivity was noted to be restricted to the basal layer cells. In contrast, CD44s and CD44v6 expression was completely absent in nearly all cases of adenomatosis. CONCLUSIONS Altered CD44s and/or CD44v6 expression appears to be a feature of all preneoplastic lesions in the lung, the precise nature of which varies according to histologic tumor type. Therefore, the authors conclude that CD44s and CD44v6 may lend themselves to be markers of preneoplastic changes in the lung. Cancer 2001;92:1231–6. © 2001 American Cancer Society.

HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4

“…However, Hoxb13 mutant mice did not reveal any phenotypes of prostatic intraepithelial neoplasia, which may require the loss of another regulatory protein, such as Nkx3.1. The missexpression of CD44 in luminal epithelial cells observed in these mice is consistent with preneoplastic lesions in many tissue types (29,30).…”

Hoxb13is required for normal differentiation and secretory function of the ventral prostate

“…Given these data, it is likely that there is a loss of identity and impaired secretory function of cells in the luminal epithelium rather than a complete transformation to a different prostatic lobe. The misexpression of CD44 on the apical surface in luminal cells in the Hoxb13 homozygous mutant ventral prostate is consistent with preneoplastic lesions in many tissue types (Sugar et al, 1997;Lagorce-Pages et al, 1998;Wimmel et al, 2001) and in prostate tumors (Paradis et al, 1998). Interestingly, loss of heterozygosity of the 17q21 locus, which spans the Hoxb cluster, in humans is linked to early events of prostate carcinogenesis such as preneoplastic lesions (Brothman et al, 1995;Brothman, 1997;Deubler et al, 1997).…”

Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

“…What pointed toward layilin as an ideal HA receptor to be involved epithelial permeability is that it is known to interact with members of the ezrin, radixin, and moesin proteins (81) that are key regulators of cytoskeletonplasma membrane interactions in polarized cell. CD44 and RHAMM are two of the better characterized HA receptors in airway epithelial cells (19,21,(82)(83)(84), but in intact epithelium CD44 expression is restricted to the basolateral domain (83,85,86) and thus, at least initially, cannot be accessed by fragments released during luminal HA degradation. RHAMM is apically expressed (19,21) but lacks a cytoplasmic domain.…”