The Molecular and Clinical Significance of Cd44 Proteolytic Cleavage in Gastrointestinal Stromal Tumors
Kai-Hsi Hsu*1,2, Yan-Shen Shan3, Hung-Wen Tsai4, Pin-Wen Lin3
1Department of Surgery, Tainan Hospital, Department of Health, Executive Yuan, ROC, Tainan, Taiwan; 2Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan, Tainan, Taiwan; 3Department of Surgery, National Cheng Kung University Medical Center, Tainan, Taiwan, Tainan, Taiwan; 4Department of Pathology, National Cheng Kung University Medical Center, Tainan, Taiwan, Tainan, Taiwan
Purpose: CD44 is a type I transmembrane protein that has been implicated in a lot of cellular activities, including cell migration, invasion and metastasis. It has been found that CD44 loss can be a poor prognostic factor in gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumor of the gastrointestinal tract. The purpose of this study is to investigate the activities of CD44 ectodomain cleavage and the putative mechanisms of CD44 protein loss in GIST.Materials and
Methods: From January 1999 to August 2007, 31 patients undergoing surgical resection for GIST in National Cheng Kung University Hospital (NCKUH) were included in this study. Clinicopathologic data of these patients were collected. Immunohistochemistry for CD44 protein, reverse transcription -polymerase chain reaction (RT-PCR) for CD44 mRNA, and Western blot for CD44 cleavage products were conducted in the tumor and normal tissues from these patients available at the NCKUH tissuebank.
Results: We previously identified loss of CD44 protein expression in GIST as a poor prognostic factor in GIST. In this study, CD44 cleavage products could be detected in the majority of GIST tumor tissues but not in most of their normal counterparts, suggesting the high prevalence of CD44 cleavage in GIST. Enhanced CD44 cleavage activities were found to be related to CD44 protein loss without concurrent CD44 mRNA loss, indicating that CD44 cleavage might play a role in the mechanism of CD44 protein loss in GIST.
Conclusion: The expression of CD44 and its cleavage have been noted to be involved in tumor invasion and metastasis. We have found that loss of CD44 expression and the associated poor clinical outcomes in GIST may be related to the increased cleavage activities of CD44, which may be the putative mechanism responsible for CD44 protein loss in GIST.
