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 journalArticlepeer-review

125 Citations (Scopus)

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
Pages (from-to)441-447
Number of pages7
JournalAmerican Journal of Pathology
Volume160
Issue number2
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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