Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors

Isamu Okamoto, Hiromasa Tsuiki, Lawrence C. Kenyon, Andrew K. Godwin, David R. Emlet, Marina Holgado-Madruga, Irene S. Lanham, Christopher J. Joynes, Kim T. Vo, Abhijit Guha, Mitsuhiro Matsumoto, Yukitaka Ushio, Hideyuki Saya, Albert J. Wong

    Research output: Contribution to journalArticle

    124 Scopus citations

    Abstract

    Cell surface adhesion molecules are crucial for the development and/or pathogenesis of various diseases including cancer. CD44 has received much interest as a major adhesion molecule that is involved in tumor progression. We have previously demonstrated that the ectodomain of CD44 undergoes proteolytic cleavage by membrane-associated metalloproteases in various tumor cell lines. The remaining membrane-bound CD44 cleavage product can be detected using antibodies against the cytoplasmic domain of CD44 (anti-CD44cyto antibody). However, the cleavage of CD44 in primary human tumors has not been investigated. Using Western blots with anti-CD44cyto antibody to assay human tumor tissues, we show that the CD44 cleavage product can be detected in 58% (42 of 72) of gliomas but not in normal brain. Enhanced CD44 cleavage was also found in 67% (28 of 42) of breast carcinomas, 45% (5 of 11) of non-small cell lung carcinomas, 90% (9 of 10) of colon carcinomas, and 25% (3 of 12) of ovarian carcinomas. Tumors expressing a CD44 splice variant showed a significantly higher incidence of enhanced CD44 cleavage. The wide prevalence of CD44 cleavage suggests that it plays an important role in the pathogenesis of human tumors.

    Original languageEnglish (US)
    Pages (from-to)441-447
    Number of pages7
    JournalAmerican Journal of Pathology
    Volume160
    Issue number2
    DOIs
    StatePublished - Jan 1 2002

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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  • Cite this

    Okamoto, I., Tsuiki, H., Kenyon, L. C., Godwin, A. K., Emlet, D. R., Holgado-Madruga, M., Lanham, I. S., Joynes, C. J., Vo, K. T., Guha, A., Matsumoto, M., Ushio, Y., Saya, H., & Wong, A. J. (2002). Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. American Journal of Pathology, 160(2), 441-447. https://doi.org/10.1016/S0002-9440(10)64863-8