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ƒAƒNƒeƒBƒuƒ{[ƒhE‚Q‚O‚O‚R”N‚UŒŽŒ¤‹†”•\‚ðs‚Á‚½Šw‰ïGƒAƒƒŠƒJ—Õ°Žîᇊw‰ï‚Q‚O‚O‚R”N‚TŒŽ‚Q‚X“ú`‚UŒŽ‚T“úiƒVƒJƒSj ƒ^ƒCƒgƒ‹GŠeŽíƒqƒgŠà‘gD‚É‚¨‚¯‚éÚ’…•ªŽqCD44‚Ì×–EŠOØ’f‚̉ðÍ ”•\ŽÒG‰ª–{@—E@Ž @@@iŒF–{‘åŠw@ŒF–{‘åŠw‘åŠw‰@ˆãŠw–òŠwŒ¤‹†•”@ŒÄ‹zŠí•a‘ÔŠw•ª–ìj AbstractG 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 Ab). However, the cleavage of CD44 in primary human tumors has not been investigated. Using Western blots with anti-CD44cyto Ab 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. |