Proteolytic Cleavage of the CD44 Adhesion Molecule in Multiple Human Tumors

• Published in: The American journal of pathology Vol. 160; no. 2; pp. 441 - 447
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.02.2002; ASIP; American Society for Investigative Pathology
• Subjects: Biological and medical sciences; Brain - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - physiopathology; Breast Neoplasms - physiopathology; Carcinogenesis, carcinogens and anticarcinogens; Colonic Neoplasms - physiopathology; Female; General aspects; Glioma - pathology; Glioma - physiopathology; Humans; Hyaluronan Receptors - metabolism; Lung Neoplasms - physiopathology; Medical sciences; Neoplasms - pathology; Neoplasms - physiopathology; Ovarian Neoplasms - physiopathology; Short Communications; Tumors; Human; Cell culture; In vivo; Proteolysis; Established cell line; Cell adhesion molecule; Cleavage; Malignant tumor; Molecular biology; Carcinogenesis; In vitro
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64863-8

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.