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Expression of CD44 variant isoforms in malignant melanoma
S Seiter1, D Schadendorf, K Herrmann
1Department of Dermatology, University Hospital, Hospitalstrasse 3, 69120 Heidelberg, Germany.
Summary
CD44 variant isoforms are expressed in nevi and melanomas, but their presence doesn't solely indicate malignant transformation. Specific variants like CD44v5 and CD44v10 may play roles in melanoma metastasis and growth.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Splice variants of the CD44 adhesion molecule (CD44v) are linked to tumor progression in various human cancers.
- Understanding CD44v expression in melanoma is crucial for deciphering melanoma development and metastasis.
Purpose of the Study:
- To investigate the expression patterns of CD44 standard form and variant isoforms (v5, v6, v7, v7-v8, v10) in melanocytes, nevi, primary melanomas, and melanoma metastases.
- To determine the correlation between CD44v expression and melanoma progression, including metastasis.
Main Methods:
- Immunohistology and fluorescence-activated cell sorting (FACS) were used to analyze surface expression of CD44 and its variant isoforms.
- Tissue samples included melanocytes, nevi, primary melanomas, cutaneous and lymph node metastases, and melanoma cell lines.
Main Results:
- Melanocytes did not express CD44 variant isoforms, while nevi, primary melanomas, and metastases showed varying degrees of CD44v5, CD44v7-v8, and CD44v10 expression.
- Exons v6 and v7 were not detected. CD44v10 was upregulated in thick tumors and skin metastases, while CD44v5 was elevated in lymph node metastases.
- CD44v5-positive melanoma lines showed metastatic potential in mice, but CD44v expression was not exclusively linked to malignancy.
Conclusions:
- CD44 variant isoform expression is present in both benign nevi and malignant melanomas, suggesting it's not solely indicative of malignant transformation or progression.
- CD44v5 upregulation in lymph node metastases may promote growth, and CD44v10 expression in nevi and thicker melanomas might facilitate tissue anchoring.