High‐level Expression of the CD44 Variant Sharing Exon v10 in Renal Cancer

Kan, Masaharu; Aki, Masashi; Akiyama, Kinya; Naruo, Seiichi; Kanayama, Hiro‐omi; Kagawa, Shunsuke

doi:10.1111/j.1349-7006.1995.tb03095.x

Cited by 24 publications

(9 citation statements)

References 20 publications

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“…Many studies have linked the expression of CD44 isoforms to tumour progression and metastatic capability in human malignant diseases, such as gastrointestinal cancer, 8,17–21 cervical cancer, 22–25 renal cancer, 26,27 non‐Hodgkin's lymphoma, 18,28–31 neuroblastoma, 32,33 and breast cancer 15,28 , 34–40 . There is also some direct experimental support for this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological associations of CD44 mRNA and protein expression in primary breast carcinomas

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Clinicopathological associations of CD44 mRNA and protein expression in primary breast carcinomas

et al. 2003

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“…It has been shown that CD44 is up‐regulated and expands its repertoire of variant isoforms in many human tumours [12–14]. Our previous study [23] showed that there are quantitative and qualitative differences in the expression of CD44 between renal cancer and normal kidney tissue, and among different renal cancer tissues. Using RT‐PCR‐Southern blot analysis, the CD44 variant sharing only exon v10 was enhanced in 71% of clear‐cell renal cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, there have been few studies of CD44 and its variants in RCC, or of their role in tumour progression. Studies to date have shown that CD44 isoform v10 (CD44v10) is expressed at high levels in renal cancer tissue [23] and there are clear differences in CD44 expression in the two major histological subtypes of RCC (clear-cell and chromophilic carcinoma) [24].…”

Section: Introductionmentioning

confidence: 99%

Analysis of CD44 isoform v10 expression and its prognostic value in renal cell carcinoma

Tsuji

Kanda

et al. 2000

BJU International

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Objective To examine the expression of CD44 isoform v10 (CD44v10) in patients with renal cell carcinoma (RCC), analyse its role in RCC and its relationship with conventional clinical-histopathological experience. Materials and methods Sixty-four RCC specimens and ®ve metastatic specimens were analysed immunohistochemically using a CD44v10 speci®c antibody. Thus the aims of the present study were to examine the correlation between the immunohistochemical expression of CD44v10 protein with conventional histopathological variables and to determine its prognostic role in patients with RCC. Materials and methodsSamples of tumour and normal foci were obtained from 64 patients (41 men and 23 women, mean age 62 years, range 23±79) with RCC who underwent radical nephrectomy. The tissue was formalin-®xed and paraf®n-embedded. The clinicopathological characteristics of tumours from all patients were classi®ed according to the general rules for clinical and pathological studies of RCC of the Japanese Urological Association and Society of Pathology (Table 1). Five metastatic lesions from the patients with RCC were also analysed, including three lymph node metastasis, one bone metastasis and one skin metastasis. The median (range) follow-up of the patients was 48.6 (2.6±105) months. Immunohistochemical stainingSections (5 mm) were stained immunohistochemically using primary antibodies directed against CD44v10 protein (Clone VFF-14, Serotec Ltd, Oxford, England, dilution 1 : 100). The procedure was modi®ed slightly from that described previously [25]. Sections were deparaf®nized in xylene and rehydrated in graded alcohols, and then autoclaved in citrate buffer for 10 min at 120uC and allowed to cool at room temperature for 40 min. Endogenous peroxidase activity was blocked by immersing sections in 0.3% hydrogen peroxide in methanol for 30 min before immunostaining. Sections were pretreated with normal rabbit serum for 5 min at room temperature and incubated overnight at 4uC with the primary antibodies in a humidi®ed chamber. Subsequently, biotinylated antirabbit and antimouse antibody (LSAB-Kit, Dako Corp., Carpinteria, CA, USA) was applied to the sections for 10 min. Streptavidin-biotinylated peroxidase complex (LSAB-Kit, Dako) was then applied and sections incubated with the chromogen diaminobenzidine (Wako, Osaka, Japan). After immunohistochemical staining, sections were counterstained with haematoxylin to enhance nuclear detection. Between all antibody incubations, sections were washed with PBS. Finally, slides were dehydrated and mounted in Permount. For the negative controls, primary antibody was substituted with PBS in duplicate sections.CD44v10 expression was evaluated using light microscopy, with cells that stained darker than the negative controls considered positive. The percentage of tumour cells positively stained was determined by counting at least 800 tumour cells in four selected ®elds that showed the highest immunoreactivity at r400 magni®cation. The immunohistochemical results were evaluated as: negative, no ...

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“…Indeed, previous studies demonstrated that exon v10 plays a role in promoting breast tumor development and progression [19], [20]. High-level expression of this exon, v10, was also reported in malignant renal cell carcinoma cells [21]. Although the mechanisms by which exon v10 facilitates these processes are not entirely clear, it is possible that this exon stimulates migration, adhesion, and growth in microenvironments through mediating the interaction with ECM directly or indirectly by forming molecular complexes with other cell surface molecules.…”

Section: Introductionmentioning

confidence: 89%

DNA Aptamers against Exon v10 of CD44 Inhibit Breast Cancer Cell Migration

et al. 2014

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CD44 adhesion molecules are expressed in many breast cancer cells and have been demonstrated to play a key role in regulating malignant phenotypes such as growth, migration, and invasion. CD44 is an integral transmembrane protein encoded by a single 20-exon gene. The diversity of the biological functions of CD44 is the result of the various splicing variants of these exons. Previous studies suggest that exon v10 of CD44 plays a key role in promoting cancer invasion and metastasis, however, the molecular mechanisms are not clear. Given the fact that exon v10 is in the ectodomain of CD44, we hypothesized that CD44 forms a molecular complex with other cell surface molecules through exon v10 in order to promote migration of breast cancer cells. In order to test this hypothesis, we selected DNA aptamers that specifically bound to CD44 exon v10 using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). We selected aptamers that inhibited migration of breast cancer cells. Co-immunoprecipitation studies demonstrated that EphA2 was co-precipitated with CD44. Pull-down studies demonstrated that recombinant CD44 exon v10 bound to EphA2 and more importantly aptamers that inhibited migration also prevented the binding of EphA2 to exon v10. These results suggest that CD44 forms a molecular complex with EphA2 on the breast cancer cell surface and this complex plays a key role in enhancing breast cancer migration. These results provide insight not only for characterizing mechanisms of breast cancer migration but also for developing target-specific therapy for breast cancers and possibly other cancer types expressing CD44 exon v10.

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High‐level Expression of the CD44 Variant Sharing Exon v10 in Renal Cancer

Cited by 24 publications

References 20 publications

Clinicopathological associations of CD44 mRNA and protein expression in primary breast carcinomas

Clinicopathological associations of CD44 mRNA and protein expression in primary breast carcinomas

Analysis of CD44 isoform v10 expression and its prognostic value in renal cell carcinoma

DNA Aptamers against Exon v10 of CD44 Inhibit Breast Cancer Cell Migration

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