Molecular studies into the role of CD44 variants in metastasis in gastric cancer

Hsieh, Hsi‐Lung; Yu, Jyh Cherng; Ho, Ling‐Jun; Chiu, Shao‐Chih; Harn, Horng Jyh

doi:10.1136/mp.52.1.25

Cited by 35 publications

(30 citation statements)

References 36 publications

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“…In 1994, Yokozaki et al [22] indicated that the detection of CD44 transcription variants can serve as a powerful tool for the diagnosis of gastric cancer. Many studies have indicated that the generation of CD44 splice variants, like V5 and V6, might be linked closely to gastric carcinoma tumorigenesis and differentiation, suggesting that these isoforms can be used as an indicator of tumor progression in the biopsies of patients with gastric carcinoma [23][24][25][26][27][28] . Moreover, it has been shown that patients with an over-expression of CD44 have a higher lymph node metastatic rate and invasion [27] .…”

Section: Discussionmentioning

confidence: 99%

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

Ghaffarzadehgan¹,

Jafarzadeh²,

Raziee³

et al. 2008

WJG

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used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P = 0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients. Abstract AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was

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Section: Discussionmentioning

confidence: 99%

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

Ghaffarzadehgan¹,

Jafarzadeh²,

Raziee³

et al. 2008

WJG

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“…CD44 (Hsieh et al, 1999), keratins 7 and 8 (Martens et al, 1999) are overexpressed in several different kinds of cancers. Galectin 4 has been found to be overexpressed in breast cancers and schirrous gastric cancer cell lines (Hippo et al, 2001;Moon et al, 2001).…”

Section: Genes Related To Cell Adhesion and Motilitymentioning

confidence: 99%

“…Overexpression or down-regulation of these genes in highly metastatic cells, as we have shown in this study, is in good concordance with the findings of previous reports (El-Rifai et al, 2001;Hippo et al, 2001) and indicates that gene expression changes in these cells accurately reflects some metastatic characteristics. For example, CD44 and galectin 3 (Hsieh et al, 1999;Moon et al, 2001), genes relevant for cancer metastasis, were up-regulated in peritoneal metastasis. Integrin b 4 has recently been reported to be a suppressor of peritoneal dissemination of gastric cancer (Ishii et al, 2000).…”

Section: Genes Related To Apoptosis and Cell Cyclementioning

confidence: 99%

Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites

et al. 2002

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Advanced gastric cancer is often accompanied by metastasis to the peritoneum, resulting in a high mortality rate. Mechanisms involved in gastric cancer metastasis have not been fully clarified because metastasis involves multiple steps and requires a combination of altered expressions of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer peritoneal dissemination. In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumour (SNU-1) and of other cell lines established from the metastasis to the peritoneal cavity (SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB). The application of a high-density cDNA microarray method made it possible to analyse the expression of approximately 21 168 genes. Our examinations of SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB showed that 24 genes were upregulated and 17 genes down-regulated besides expression sequence tags. The analysis revealed the following altered expression such as: (a) up-regulation of CD44 (cell adhesion), keratins 7, 8, and 14 (epitherial marker), aldehyde dehydrogenase (drug metabolism), CD9 and IP3 receptor type3 (signal transduction); (b) down-regulation of IL2 receptor g, IL4-Stat (immune response), p27 (cell cycle) and integrin b4 (adhesion) in gastric cancer cells from malignant ascites. We then analysed eight gastric cancer cell lines with Northern blot and observed preferential up-regulation and down-regulation of these selected genes in cells prone to peritoneal dissemination. Reverse transcriptase -polymerase chain reaction confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination, promise to provide a new insight into the study of human gastric cancer peritoneal dissemination.

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“…Although RNA splicing is essential in generating protein diversity, which is important in biological functions, alternative RNA processing has been witnessed in human cancer during transformation and/or acquisition of metastasis (Hsieh et al, 1999;Philips and Cooper, 2000;Poola and Speirs, 2001;Bracco and Kearsey, 2003;Faustino and Cooper, 2003;Agrawal and Eng, 2006). Therefore, the possible occurrence of different splice variants (SV) and the probable association with the risk of developing cancer have stimulated researchers to study the fundamental impact of various splicing alterations on the behaviour of the protean presentations of CS, CS-like and BRRS (Poola and Speirs, 2001;Bracco and Kearsey, 2003;Faustino and Cooper, 2003;Agrawal and Eng, 2006).…”

Section: Pten Splice Variants and Possible Role In Cs Phenotypementioning

confidence: 99%

Genetic and phenotypic heterogeneity in the PTEN hamartoma tumour syndrome

2008

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Molecular studies into the role of CD44 variants in metastasis in gastric cancer

Cited by 35 publications

References 36 publications

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites

Genetic and phenotypic heterogeneity in the PTEN hamartoma tumour syndrome

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