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

123 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
Publication statusPublished - 2002
Externally publishedYes

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Neoplasms
Anti-Idiotypic Antibodies
Carcinoma
Membranes
Cell Adhesion Molecules
Metalloproteases
Tumor Cell Line
Non-Small Cell Lung Carcinoma
Glioma
Colon
Western Blotting
Breast Neoplasms
Antibodies
Incidence
Brain

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Okamoto, I., Tsuiki, H., Kenyon, L. C., Godwin, A. K., Emlet, D. R., Holgado-Madruga, M., ... Wong, A. J. (2002). Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. American Journal of Pathology, 160(2), 441-447.

Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. / Okamoto, Isamu; Tsuiki, Hiromasa; Kenyon, Lawrence C.; Godwin, Andrew K.; Emlet, David R.; Holgado-Madruga, Marina; Lanham, Irene S.; Joynes, Christopher J.; Vo, Kim T.; Guha, Abhijit; Matsumoto, Mitsuhiro; Ushio, Yukitaka; Saya, Hideyuki; Wong, Albert J.

In: American Journal of Pathology, Vol. 160, No. 2, 2002, p. 441-447.

Research output: Contribution to journalArticle

Okamoto, I, Tsuiki, H, Kenyon, LC, Godwin, AK, Emlet, DR, Holgado-Madruga, M, Lanham, IS, Joynes, CJ, Vo, KT, Guha, A, Matsumoto, M, Ushio, Y, Saya, H & Wong, AJ 2002, 'Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors', American Journal of Pathology, vol. 160, no. 2, pp. 441-447.
Okamoto I, Tsuiki H, Kenyon LC, Godwin AK, Emlet DR, Holgado-Madruga M et al. Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. American Journal of Pathology. 2002;160(2):441-447.
Okamoto, Isamu ; Tsuiki, Hiromasa ; Kenyon, Lawrence C. ; Godwin, Andrew K. ; Emlet, David R. ; Holgado-Madruga, Marina ; Lanham, Irene S. ; Joynes, Christopher J. ; Vo, Kim T. ; Guha, Abhijit ; Matsumoto, Mitsuhiro ; Ushio, Yukitaka ; Saya, Hideyuki ; Wong, Albert J. / Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. In: American Journal of Pathology. 2002 ; Vol. 160, No. 2. pp. 441-447.
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