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

Ghaffarzadehgan, Kamran; Jafarzadeh, Mostafa; Raziee, Hamid; Sima, Hamid Reza; Shandiz, Ehsan Esmaili; Hosseinnezhad, Hanieh; Taghizadeh-Kermani, Ali; Moaven, Omeed; Bahrani, Maryam

doi:10.3748/wjg.14.6376

Cited by 55 publications

(42 citation statements)

References 27 publications

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“…However, in the present study, nested RT-PCR was combined with immunohistochemical analysis of 76 cases of gastric carcinoma and 12 cases of atypical hyperplasia. The positive rate of CD44v reported using nested RT-PCR in the present study was significantly higher than the positive rates detected in previous studies (9,10,25,30), however, the possibility of false positives was not considered. Furthermore, the use of RT-PCR with nested PCR as opposed to Southern blot hybridization resulted in experimental results that were confirmed by DNA sequencing.…”

Section: Discussioncontrasting

confidence: 55%

“…Furthermore, abnormal expression of CD44 mRNA was determined to be relatively high irrespective of whether the gastric carcinoma tissues were highly or poorly differentiated (24,25). A number of studies have proposed that the role of CD44v in enhancing the infiltration and metastasis of tumor cells may be associated with its ability to alter the structure and function of cell surface adhesion molecules (10,26). Miwa et al (27) revealed that gastric carcinoma tissues exhibited higher CD44v expression compared with that of adjacent healthy tissues, with 76.6% (23/30 cases) positive expression.…”

Section: Discussionmentioning

confidence: 99%

“…Among these CD44 variants, CD44v8-10 expression is considered to be a prognostic indicator of gastric carcinoma (9). A previous study of gastric cancer evaluated the expression of standard CD44 (CD44s) (10), while other studies have investigated the expression of the CD44v8-10 isoform or CD44s and Rapid and reliable detection of CD44 variants in gastric carcinoma using a nested reverse transcription-polymerase chain reaction . The study utilized antibodies against CD44s, an isoform lacking all variant exons that is widely expressed in lymphoid and non-lymphoid tissues.…”

Section: Introductionmentioning

confidence: 99%

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Rapid and reliable detection of CD44 variants in gastric carcinoma using a nested reverse transcription-polymerase chain reaction

2015

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Abstract. The present study aimed to establish a rapid and reliable method for detecting the expression of cluster of differentiation 44 variant (CD44v) in gastric carcinoma, and to investigate the significance of CD44v in gastric carcinoma. Using a nested reverse transcription-polymerase chain reaction (RT-PCR) technique, the expression of CD44v and CD44v8-10 was analyzed in gastric cancer tissues (128 cases), precancerous lesions (19 cases of atypical hyperplasia and 6 cases of intestinal metaplasia) and corresponding adjacent non-cancerous tissues (153 cases). The tumor and non-cancerous biopsy samples of 153 patients were analyzed using nested RT-PCR. All the PCR products included bands at 482 bp, demonstrating positive CD44 expression. By contrast, the CD44v band (>600 bp) was observed in 132/153 total tumor samples (86.3%), including 114/128 gastric cancer samples (89.1%), 16/19 atypical hyperplasia samples (84.2%) and 2/6 intestinal metaplasia samples (33.3%). However, 18/153 non-cancerous tissues samples (11.8%) exhibited a CD44v band. Thus, CD44v expression was significantly higher in gastric cancer tissues and precancerous lesions compared with that of adjacent non-cancerous tissues (P<0.05). Furthermore, there was a significant difference in CD44v8-10 expression detected between gastric cancer and adjacent non-cancerous tissue samples (P<0.05). Among the 25 patients with precancerous lesions, 8/19 atypical hyperplasia cases and 1/6 intestinal metaplasia cases were positive for CD44v8-10 expression. The difference in the CD44v8-10 expression rate among the various pathological types of gastric cancer (n=128) cases was not significant (P>0.05). Additionally, immunohistochemical analysis identified CD44v positivity (++) in 59/76 (77.6%) cases of gastric cancer and 5/12 (41.1%) cases of atypical hyperplasia. The CD44v and CD44v8-10 PCR products were confirmed by sequencing analysis. The results of the present study indicated that nested RT-PCR technology may be exploited as a method for gastric carcinoma diagnosis.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid and reliable detection of CD44 variants in gastric carcinoma using a nested reverse transcription-polymerase chain reaction

2015

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“…Since then, most reports described the expression of CD44 variants and their association with the distinct histotypes of this neoplasia in comparison with normal mucosa, without further considerations. [15][16][17][18][19][20] In this study we aimed to dissect the splicing pattern of CD44 in gastric neoplasm in comparison to normal stomach. The expression of relevant splicing forms was further quantified and compared with that of normal gastric mucosa, in terms of RNA and protein, in distinct lesions and stages of GC development: GC cell lines, primary premalignant lesions and malignant gastric lesions (sporadic and hereditary forms).…”

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confidence: 99%

De novo expression of CD44 variants in sporadic and hereditary gastric cancer

Cunha

Oliveira

Wen

et al. 2010

Laboratory Investigation

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CD44 is the major ubiquitously expressed cell surface receptor for hyaluronate. The CD44 gene encodes several protein isoforms due to extensive alternative splicing and post-translational modifications. Some of these CD44 variable isoforms have been foreseen as key players in malignant transformation and their expression is highly restricted and highly specific, unlike the canonical CD44 standard isoform. In this study, we aimed at dissecting the mRNA splicing pattern of CD44 in normal stomach and gastric cancer (GC) cell lines (n ¼ 9) using cloning and quantitative mRNA amplification assays. Moreover, we assessed the RNA levels and protein expression pattern of relevant splicing forms in distinct premalignant and malignant gastric lesions (sporadic (n ¼ 43) and hereditary (n ¼ 3) forms) using real-time RT-PCR and immunohistochemistry. We also explored the association of CD44 and E-cadherin expression by immunohistochemistry, as E-cadherin has a pivotal functional role in GC. We established the pattern of CD44 variant forms in normal stomach and gastric malignancy. We observed that although exon v6-containing isoforms were rarely expressed in normal gastric mucosa, they became increasingly expressed both in gastric premalignant (hyperplastic polyps, complete and incomplete intestinal metaplasia, low-and high-grade dysplasia) and malignant lesions (cell lines derived from GCs, primary sporadic GCs and hereditary diffuse GCs (HDGCs)). Moreover, we verified that whenever E-cadherin expression was absent, exon v6-containing CD44 isoforms were overexpressed. The lack of expression of CD44 isoforms containing exon v6 in the surface and foveolar epithelia of normal stomach and, its de novo expression in premalignant, as well as in sporadic and hereditary malignant lesions of the stomach, pinpoint CD44 v6-containg isoforms as potential biomarkers for early transformation of the gastric mucosa. Further, our results raise the hypothesis of using CD44v6 as a marker of early invasive intramucosal carcinoma in HDGC CDH1 mutation carriers that lack CDH1 expression in their tumors.

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“…In gastric adenocarcinoma, CD44 is highly expressed and is correlated with a poor prognosis in patients with the intestinal disease type (44). In a previous study, we reported that the regulation of matrix metalloproteinase-9, intercellular adhesion medlecule-1 and E-Cadherin expression may be one of the potential molecule mechanisms for IL-8-induced adhesion, migration and invasion in gastric cancer (16).…”

mentioning

confidence: 99%

Low-dose interleukin-8 induces the adhesion, migration and invasion of the gastric cancer SGC-7901 cell line

Shi

Wei

2015

Oncology Letters

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Abstract. , an important inflammatory cytokine, is strongly associated with gastric cancer development and metastasis. High-dose (>1 ng/ml) IL-8 has been revealed to promote the adhesion, migration and invasion of human gastric cancer SGC-7901 cells in a dose-dependent manner. However, the IL-8 level produced by gastric cells is marginal, at even less than 1 ng/ml. It is unclear whether low-dose IL-8 also induces these capacities. In the present study, the effect of low-dose IL-8 on the adhesion, migration and invasion of the SGC-7901 cell line and the underlying molecular mechanism with regard to cluster of differentiation 44 (CD44) were investigated. The SGC-7901 cells were exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1 ng/ml) in vitro. The adhesion of the SGC-7901 cells to fibronectin, an extracellular matrix component, was then detected by cell counting kit 8 assay. Migration and invasion abilities were evaluated by wound scratch and Transwell chamber assays. In addition, protein and mRNA levels of CD44 were measured using immunofluorescence and western blotting, and quantitative polymerase chain reaction, respectively, in cells cultured for 72 h. Following the exposure of the SGC-7901 cells to the various low doses of IL-8, the cell adhesion, migration and invasion capacities were promoted by IL-8, but not in a significant dose-dependent manner. Low-dose IL-8 upregulated the protein and mRNA expression of CD44. In conclusion, low-dose IL-8 potently induces the adhesion, migration and invasion of SGC-7901 cells, and the regulation of CD44 expression is one of the potential molecular mechanisms involved.

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

Cited by 55 publications

References 27 publications

Rapid and reliable detection of CD44 variants in gastric carcinoma using a nested reverse transcription-polymerase chain reaction

Rapid and reliable detection of CD44 variants in gastric carcinoma using a nested reverse transcription-polymerase chain reaction

De novo expression of CD44 variants in sporadic and hereditary gastric cancer

Low-dose interleukin-8 induces the adhesion, migration and invasion of the gastric cancer SGC-7901 cell line

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