Isolation of All CD44 Transcripts in Human Epidermis and Regulation of Their Expression by Various Agents

Abstract

CD44, a cell surface proteoglycan, is involved in many biological events. CD44 transcripts undergo complex alternative splicing, resulting in many functionally distinct isoforms. To date, however, the nature of these isoforms in human epidermis has not been adequately determined. In this study, we isolated all CD44 transcripts from normal human epidermis, and studied how their expressions are regulated. By RT-PCR, we found that a number of different CD44 transcripts were expressed in human epidermis, and we obtained all these transcripts from DNA bands in agarose and acrylamide gels by cloning. Detailed sequence analysis revealed 18 CD44 transcripts, 3 of which were novel. Next, we examined effects of 10 different agents on the expression of CD44 transcripts in cultured human keratinocytes, and found that several agents, particularly epidermal growth factor, hydrogen peroxide, phorbol 12-myristate 13-acetate, retinoic acid, calcium and fetal calf serum differently regulated their expressions in various patterns. Furthermore, normal and malignant keratinocytes were found to produce different CD44 transcripts upon serum stimulation and subsequent starvation, suggesting that specific CD44 isoforms are involved in tumorigenesis via different CD44-mediated biological pathways.

Overexpression of CD44 Variant 9: A Novel Cancer Stem Cell Marker in Human Cholangiocarcinoma in Relation to Inflammation

“…In multiple complexes of variant isoforms, the exon combination of variable regions provides a heterogeneity of CD44 molecules. In exon combination, isoforms of CD44 include a property of tissue-specific expression by distinct expression in different tissues with normal or diseased states [ 22 ]. These combinations predominantly are exhibited in specialized tissues, e.g., CD44v3-10 is a keratinocyte form and CD44v8-10 is an epithelial form [ 23 – 25 ].…”

Ovarian Cancer Stem Cells: Unraveling a Germline Connection

“…[64][65][66] is strongly implicated in ovarian epithelial biology [67] and it is speculated that neoplastic transformation of these LGR5 + stem cells would lead to ovarian cancer [7,68]. CD44 is known to regulate key processes like cell adhesion, migration, tight junction assembly, recirculation and homing of lymphocytes, hematopoiesis, and angiogenesis [69] and was expressed with pluripotent marker SSEA4 [70] and associated with highly metastatic tumors and poor prognosis in patients [71].…”

CD44 expression in human skin: High expression in irritant and allergic contact dermatitis and moderate expression in psoriasis lesions in comparison with healthy controls

“…According to previous immunofluorescent skin analysis, the basic (standard) CD44s form is most pronounced in the epidermis and dermis, whereas its v6 and v9 forms are more pronounced only in the epidermis. 30 Although we did not specifically look at the different CD44 forms, based on previous experience and research, we assume that the CD44v6 and v9 forms were those that were statistically significantly more pronounced in the epidermis of ICD lesions.…”