Clinical Implication and Mitotic Effect of CD44 Cleavage in Relation to Osteopontin/CD44 Interaction and Dysregulated Cell Cycle Protein in Gastrointestinal Stromal Tumor

被引:11
|
作者
Hsu, Kai-Hsi [1 ,2 ]
Tsai, Hung-Wen [1 ,3 ]
Lin, Pin-Wen [4 ]
Hsu, Yun-Shang [5 ]
Shan, Yan-Shen [1 ,4 ]
Lu, Pei-Jung [1 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 70101, Taiwan
[2] Tainan Hosp, Dept Hlth, Dept Surg, Tainan, Taiwan
[3] Natl Cheng Kung Univ, Coll Med, Dept Pathol, Tainan 70101, Taiwan
[4] Natl Cheng Kung Univ, Coll Med, Dept Surg, Tainan 70101, Taiwan
[5] So Taiwan Univ Technol, Dept Biotechnol, Tainan, Taiwan
关键词
CANCER STEM-CELLS; PROGNOSTIC-SIGNIFICANCE; REGULATORY PROTEINS; ACTIVATION; EXPRESSION; PROGRESSION; HYALURONAN; CARCINOMA; PATHWAY; TRANSFORMATION;
D O I
10.1245/s10434-010-0927-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
CD44 and osteopontin (OPN) are functionally related molecules that, alone or in combination, play miscellaneous biological and pathophysiologic roles. CD44 cleavage, one unique feature of CD44, occurs in human cancers, but its function remains unclear. This study aimed to assess the clinicopathologic significance and mechanism of CD44 cleavage in gastrointestinal stromal tumor (GIST) with respect to OPN and OPN/CD44 interaction. CD44 cleavage was evaluated by immunoblotting in 31 primary GIST tumor specimens with paired normal tissues. OPN/CD44 interaction was examined by in situ proximity ligation assay. The associations of CD44 cleavage activity with clinicopathologic parameters, cyclin D1 expression, beta-catenin expression, OPN expression, and OPN/CD44 interaction were analyzed. CD44 cleavage activity was demonstrated in 87.1% of GIST, in contrast to its absence in normal tissues. Increased CD44 cleavage activity was significantly associated with enhanced mitosis by multivariate analysis, in addition to being related to tumor size, recurrence, high-risk status, and poor survival by univariate analysis. Mitosis was significantly higher in GIST with increased CD44 cleavage activity, which also positively correlated with tumor-specific beta-catenin and cyclin D1 overexpression, indicating a mitotic effect through aberrant cell cycle. Both OPN and OPN/CD44 interactions were significantly associated with CD44 cleavage. Our study demonstrates the clinicopathological significance of CD44 cleavage in GIST. There is a significantly increased mitosis associated with CD44 cleavage in relation to OPN/CD44 interaction and dysregulated cell cycle in GIST.
引用
收藏
页码:2199 / 2212
页数:14
相关论文
共 50 条
  • [1] Clinical Implication and Mitotic Effect of CD44 Cleavage in Relation to Osteopontin/CD44 Interaction and Dysregulated Cell Cycle Protein in Gastrointestinal Stromal Tumor
    Kai-Hsi Hsu
    Hung-Wen Tsai
    Pin-Wen Lin
    Yun-Shang Hsu
    Yan-Shen Shan
    Pei-Jung Lu
    Annals of Surgical Oncology, 2010, 17 : 2199 - 2212
  • [2] The molecular and clinical significance of CD44 proteolytic cleavage in gastrointestinal stromal tumors
    Hsu, Kai-Hsi
    Shan, Yan-Shen
    Tsai, Hung-Wen
    Lin, Pin-Wen
    GASTROENTEROLOGY, 2008, 134 (04) : A909 - A909
  • [3] Engagement of CD44 promotes Rac activation and CD44 cleavage during tumor cell migration
    Murai, T
    Miyazaki, Y
    Nishinakamura, H
    Sugahara, KN
    Miyauchi, T
    Sako, Y
    Yanagida, T
    Miyasaka, M
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) : 4541 - 4550
  • [4] Osteopontin Expression is an Independent Adverse Prognostic Factor in Resectable Gastrointestinal Stromal Tumor and its Interaction with CD44 Promotes Tumor Proliferation
    Kai-Hsi Hsu
    Hung-Wen Tsai
    Pin-Wen Lin
    Yun-Shang Hsu
    Yan-Shen Shan
    Pei-Jung Lu
    Annals of Surgical Oncology, 2010, 17 : 3043 - 3052
  • [5] Osteopontin Expression is an Independent Adverse Prognostic Factor in Resectable Gastrointestinal Stromal Tumor and its Interaction with CD44 Promotes Tumor Proliferation
    Hsu, Kai-Hsi
    Tsai, Hung-Wen
    Lin, Pin-Wen
    Hsu, Yun-Shang
    Shan, Yan-Shen
    Lu, Pei-Jung
    ANNALS OF SURGICAL ONCOLOGY, 2010, 17 (11) : 3043 - 3052
  • [6] CD44 as the prognostic factor gastrointestinal leiomyogenic tumor
    Takeuchi, H
    Tanakaya, K
    Murakami, I
    Yunoki, Y
    Yasui, Y
    Konaga, E
    GASTROENTEROLOGY, 1997, 112 (04) : A666 - A666
  • [7] Osteopontin and CD44 protein and mRNA expression in colorectal adenocarcinoma
    Kim, Jung Yeon
    Shin, Eunah
    Kim, Hyun-Jung
    Park, Kyeongmee
    Bae, Byung-Noe
    Kim, Kyoung-Soo
    VIRCHOWS ARCHIV, 2007, 451 (02) : 215 - 215
  • [8] Significance of CD44 Expression in Gastrointestinal Stromal Tumors in Relation to Disease Progression and Survival
    Kai-Hsi Hsu
    Hung-Wen Tsai
    Yan-Shen Shan
    Pin-Wen Lin
    World Journal of Surgery, 2007, 31 : 1438 - 1444
  • [9] Significance of CD44 expression in gastrointestinal stromal tumors in relation to disease progression and survival
    Hsu, Kai-Hsi
    Tsai, Hung-Wen
    Shan, Yan-Shen
    Lin, Pin-Wen
    WORLD JOURNAL OF SURGERY, 2007, 31 (07) : 1438 - 1444
  • [10] Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells
    Sugahara, KN
    Murai, T
    Nishinakamura, H
    Kawashima, H
    Saya, H
    Miyasaka, M
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) : 32259 - 32265