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(American Journal of Pathology. 2002;160:441-447.)
© 2002 American Society for Investigative Pathology

Short Communications

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^** and Albert J. Wong^*

From the Department of Microbiology and Immunology,^*
Kimmel Cancer Institute, and the Department of Pathology, Anatomy, andCell Biology,
Thomas Jefferson University,Philadelphia, Pennsylvania; the Department of MedicalOncology,
Fox Chase Cancer Center,Philadelphia, Pennsylvania; the Arthur and Sonia Labatt Brain TumorResearch Centre,^¶
The Hospital for Sick Children,Toronto, Ontario, Canada; and the First Department of InternalMedicine^||
and the Departments ofNeurosurgery
and Tumor Genetics andBiology,^**
Kumamoto University School ofMedicine, Kumamoto, Japan

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.

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