title: Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors.
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.
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Institute, BLSB 2002, Thomas Jefferson University, 233 S. 10th St., Philadelphia, PA 19107, USA.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsuiki
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Kenyon
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: David R
authors.initials: DR
authors.lastname: Emlet
authors.forename: Marina
authors.initials: M
authors.lastname: Holgado-Madruga
authors.forename: Irene S
authors.initials: IS
authors.lastname: Lanham
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Joynes
authors.forename: Kim T
authors.initials: KT
authors.lastname: Vo
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Ushio
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Wong
mesh_terms: D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology*; D001943:Breast Neoplasms / Q000503:physiopathology; D003110:Colonic Neoplasms / Q000503:physiopathology; D005260:Female; D005910:Glioma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008175:Lung Neoplasms / Q000503:physiopathology; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D010051:Ovarian Neoplasms / Q000503:physiopathology
chemical_list: D018960:Hyaluronan Receptors