Expression of CD44 splice variants in human skin and epidermal tumours

Abstract

Splice variants of the adhesion molecule CD44 (CD44v) are important in the lymphatic spread of rat carcinoma cells. In several human tumours expression of CD44v correlates with tumour progression. However, little is known about the physiological functions of distinct variant exons. Here we report on the immunohistological evaluation of CD44 expression in normal human skin and epidermal tumours which do not metastasise, or do so vary rarely. Frozen tissues were stained with a panel of monoclonal antibodies, recognizing epitopes of the CD44 standard isoform, as well as of variant exons v5, v6, v7, v7-v8 and v10. Stratum basale and spinosum as well as the root shaft of hairs reacted strongly with the whole panel of anti-CD44 antibodies. Stratum corneum, acinar cells of sebaceous and eccrine sweat glands stained with anti-CD44v5, anti-CD44v6 and anti-CD44v7, but not with anti-CD44v10, the latter recognizing the "epithelial isoform" (CD44v8-v10) of CD44. Ductal cells of glands and apocrine glands did not express CD44v. Compared with its expression in normal human skin, CD44v expression was reduced in basal cell carcinoma and squamous cell carcinoma of the skin. This was particularly true of CD44v10. The expression of CD44v in normal skin and dermal appendages indicates that not all combinations of variant exons are involved in tumour progression. Since the epithelial isoform is particularly downregulated in basal cell carcinoma and squamous cell carcinoma of the skin, it is unlikely that exons v8-v10 play a role in tumour progression. Rather, they may be of functional importance in maintenance of the epidermal structure.

CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: Assessment by the use of tissue microarray

“…10 The evidence relating to splice variants is conflicting; with different studies detecting widely varying expression levels of splice variants. 20,21 Little information relating to splice variant v3 and melanoma is available mainly because of limited detection of expression.…”

“…Clark's levels), rather than Breslow thickness. 18,19 Although various splice variants, including v5, v7, v8 and v10, have been reported as being involved in melanoma progression, 20,21 the data regarding the v3 splice variant is as yet unconvincing. 18,21 The advent of tissue microarray technology has enabled highthroughput screening to ascertain patterns of protein expression in a large number of tissue specimens simultaneously, 22 overcoming some of the time consuming aspects of conventional immunohistochemistry.…”

Identification of Specific Chondroitin Sulfate Species in Cutaneous Autoimmune Disease

“…Wide and short horizontal bars represent mean and SEM, respectively, of experiments performed in triplicate. (Leigh et al 1996;Seiter et al 1996Seiter et al , 1998 and displayed strong epidermal expression, particularly within the basal layer and stratum spinosum, with little dermal matrix expression beyond staining of infiltrating leukocytes (Fig. 4).…”

Isolation of all CD44 transcripts in human epidermis and regulation of their expression by various agents

“…Previous studies by immunohistochemistry and RT-PCR suggested that some specific isoforms of CD44 correlate with clinicopathological data and are involved in tumorigenesis of skin [42,43]. In our study, we have defined the exact compositions of all CD44 exons in epidermal keratinocytes.…”

“…(ii) CD44 isoforms are suggested to be involved in epidermal tumorigenesis and stem cell regulation [41][42][43]. (iii) We are currently studying the exact nature and expression of a novel keratinocyte antigen, desmosealin, which we believe being related to the CD44 family of proteoglycans [44].…”