Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors.
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.
Okamoto
Isamu
I
Department of Microbiology and Immunology, Kimmel Cancer Institute, BLSB 2002, Thomas Jefferson University, 233 S. 10th St., Philadelphia, PA 19107, USA.
Tsuiki
Hiromasa
H
Kenyon
Lawrence C
LC
Godwin
Andrew K
AK
Emlet
David R
DR
Holgado-Madruga
Marina
M
Lanham
Irene S
IS
Joynes
Christopher J
CJ
Vo
Kim T
KT
Guha
Abhijit
A
Matsumoto
Mitsuhiro
M
Ushio
Yukitaka
Y
Saya
Hideyuki
H
Wong
Albert J
AJ
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
D018960:Hyaluronan Receptors