Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy

Shimada, Shuichi; Ito, Akihiro; Kawasaki, Yoshihide; Kakoi, Narihiko; Taima, Takenobu; Mitsuzuka, Koji; Watanabe, Mika; Saitoh, Sei–Ichi; Arai, Yoichi

doi:10.1038/pcan.2014.9

Cited by 12 publications

(14 citation statements)

References 28 publications

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“…Previous studies showed associations between glycolipids and malignant potential of melanomas, breast cancers, and prostate cancers . In accordance, glycolipids were expressed on various cell surfaces, and their glycan structures were modified by several glycosyltransferases.…”

Section: Discussionsupporting

confidence: 56%

“…Previous studies showed associations between glycolipids and malignant potential of melanomas, (34) breast cancers, (35,36) and prostate cancers. (37) In accordance, glycolipids were expressed on various cell surfaces, and their glycan structures were modified by several glycosyltransferases. Moreover, these glycolipids regulated not only cell-cell interactions by glycan-glycan interactions (38) but also regulated cell adhesion and migration by glycolipid-tetraspanin or glycolipid-caveola interactions.…”

Section: Discussionmentioning

confidence: 99%

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I‐branching N‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling

et al. 2016

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Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I‐branching N‐acetylglucosaminyltransferase (GCNT2) converts linear i‐antigen to I‐branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin‐embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2‐positive cells were significantly lesser in organ‐confined disease than in that with extra‐capsular extensions, and GCNT2‐negative tumors were associated with significantly better prostate‐specific antigen‐free survival compared with GCNT2‐positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 regulated the expression of cell surface I‐antigen on the O‐glycan and glycolipid. Moreover, I‐antigen‐bearing glycolipids were subject to α5β1 integrin–fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT2 expression is closely associated with invasive potential of PCa.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

I‐branching N‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling

et al. 2016

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“…Gangliosides are considered attractive targets for the generation of new antitumor molecules (Doronin et al, 2014;Shimada et al, 2014). mAb-based anticancer therapies are increasingly being tested to obtain an effective immune response against cancer cells (Reichert, 2014).…”

Section: Discussionmentioning

confidence: 99%

Antitumor and cytotoxic properties of a humanized antibody specific for the GM3(Neu5Gc) ganglioside

et al. 2015

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“…In our recent report, immunohistochemical analysis of 130 radical prostatectomy specimens revealed that DSGb5 expression was significantly correlated with lymphovascular invasion of prostate cancer cells (Shimada et al 2014). In the process of cancer metastasis, lymphovascular invasion is the critical step occurring subsequent to cellular migration.…”

Section: Discussionmentioning

confidence: 99%

Ganglioside, Disialosyl Globopentaosylceramide (DSGb5), Enhances the Migration of Renal Cell Carcinoma Cells

Kawasaki

Ito

Kakoi

et al. 2015

Tohoku J. Exp. Med.

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About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon initial presentation. However, the molecular basis for RCC metastasis is not fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was originally isolated from RCC tissue extracts, and its expression is correlated with RCC metastatic potential. DSGb5 is synthesized by GalNAc α2,6-sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells. Importantly, DSGb5 binds to sialic acidbinding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity. However, the role of DSGb5 in RCC progression remains obscure. To address this issue, we used ACHN cells derived from malignant pleural effusion of a patient with metastatic RCC. Using the limiting dilution method, we isolated three independent clones with different DSGb5 expression levels. Comparison of these clones indicated that the cloned cells with high DSGb5 expression levels exhibited greater migration potential, compared to the clone with low DSGb5 expression levels. In contrast, DSGb5 expression levels exerted no significant effect on cell proliferation. We then established the ACHN-derived cell lines that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA. Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We thus demonstrated the significantly decreased migration potential of the ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the control siRNA-transfected cells expressing high DSGb5 levels, but no significant difference in the cell proliferation. Thus, DSGb5 expression may ensure the migration of RCC cells. We propose that DSGb5 expressed on RCC cells may determine their metastatic capability.

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Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy

Abstract: 5F3 expression reflects the clinical and pathological features of prostate cancer and is correlated with the outcomes following RP. Further studies are necessary to clarify the functional roles of DSGb5 and establish a novel biomarker for prostate cancer.

Cited by 12 publications

References 28 publications

I‐branching N‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling

I‐branching N‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling

Antitumor and cytotoxic properties of a humanized antibody specific for the GM3(Neu5Gc) ganglioside

Ganglioside, Disialosyl Globopentaosylceramide (DSGb5), Enhances the Migration of Renal Cell Carcinoma Cells

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