Changes in glycolipid expression in human testicular tumor

Οhyama, Chikara; Fukushi, Yasuo; Satoh, Makoto; Saitoh, Sei–Ichi; Orikasa, Seiichi; Nudelman, Edward; Straud, Mark; Hakomori, Sen‐itiroh

doi:10.1002/ijc.2910450610

Cited by 53 publications

(40 citation statements)

References 22 publications

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“…Elevated expression of Gb 3 was also detected in astrocytoma cell lines (32) and in several highly metastatic types of human tumors, including ovarian and breast cancers (33). Significant Gb 3 accumulation was also previously reported in testicular seminoma, which correlated with the metastatic potential (34,35). These data support our finding that Gb 3 expression is a marker for colonic epithelial tumor cell transformation from primary cancer into the metastatic stage and indicate that several types of invasive tumors may have common mechanisms for metastasis.…”

Section: Discussionsupporting

confidence: 92%

The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

Kovbasnjuk

Mourtazina

Baibakov

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

179

183

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The most devastating aspect of cancer is the emergence of metastases. Thus, identification of potentially metastatic cells among a tumor cell population and the underlying molecular changes that switch cells to a metastatic state are among the most important issues in cancer biology. Here we show that, although normal human colonic epithelial cells lack the glycosphingolipid globotriaosylceramide (Gb3), this molecule is highly expressed in metastatic colon cancer. In addition, a subpopulation of cells that are greatly enriched in Gb3 and have an invasive phenotype was identified in human colon cancer cell lines. In epithelial cells in culture, Gb3 was necessary and sufficient for cell invasiveness. Transfection of Gb3 synthase, resulting in Gb3 expression in noncancerous polarized epithelial cells lacking endogenous Gb3, induced cell invasiveness. metastases ͉ invasion ͉ filopodia C olorectal cancer is the second leading cause of cancer death in the U.S. (1, 2). The high mortality associated with colorectal cancer is related to its ability to spread beyond the large intestine and to invade distant organs. One route to improve understanding of the molecular mechanisms of metastasis is by the identification of genes that are differently expressed during cancer progression and͞or are responsible for acquisition of the metastatic phenotype. Although many molecular factors have been identified as contributing to metastases and represent potential targets for treatment (3), much remains to be learned about the biology of the metastatic process. Aberrant glycosylation, which has been observed in essentially all types of human cancers during cancer progression into the metastatic stage, is an example of a metastases-related

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Section: Discussionsupporting

confidence: 92%

The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

Kovbasnjuk

Mourtazina

Baibakov

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

179

183

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“…The decisive requirement for application of STxB is the cellspecific expression of Gb 3 in tumor cells: Gb3 is expressed by Burkitt and centrofollicular lymphoma and solid tumors like testicular seminoma, breast, ovary, pancreatic, and colon cancer (5,6,8,(19)(20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit

Geyer

Maak

Nitsche

et al. 2016

Molecular Cancer Therapeutics

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“…Over the last years, several groups have reported that the glycosphingolipid globotriaosyl ceramide (Gb 3 or CD77), like other glycosphingolipids (2,3), is expressed in human malignancies. Gb 3 expression has been shown in Burkitt's and centrofollicular lymphomas (4 -7), in a wide range of solid tumors such as breast and ovarian carcinomas (8,9), and in testicular seminomas (10). Moreover, it was recently reported that Gb 3 expression in human colorectal cancer correlates with invasiveness and the ability to form metastasis (11).…”

Section: Introductionmentioning

confidence: 99%

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Falguières

Maak

Weyhern

et al. 2008

Molecular Cancer Therapeutics

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The targeting of solid tumors requires delivery tools that resist intracellular and extracellular inactivation, and that are taken up specifically by tumor cells. We have shown previously that the recombinant nontoxic B-subunit of Shiga toxin (STxB) can serve as a delivery tool to target digestive tumors in animal models. The aim of this study was to expand these experiments to human colorectal cancer. Tissue samples of normal colon, benign adenomas, colorectal carcinomas, and liver metastases from 111 patients were obtained for the quantification of the expression of the cellular STxB receptor, the glycosphingolipid globotriaosyl ceramide (Gb 3 or CD77). We found that compared with normal tissue, the expression of Gb 3 was strongly increased in colorectal adenocarcinomas and their metastases, but not in benign adenomas. Short-term primary cultures were prepared from samples of 43 patients, and STxB uptake was studied by immunofluorescence microscopy. Of a given tumor sample, on average, 80% of the cells could visibly bind STxB, and upon incubation at 37°C, STxB was transported to the Golgi apparatus, following the retrograde route. This STxB-specific intracellular targeting allows the molecule to avoid recycling and degradation, and STxB could consequently be detected on tumor cells even 5 days after initial uptake. In conclusion, the targeting properties of STxB could be diverted for the delivery of contrast agents to human colorectal tumors and their metastases, whose early detection and specific targeting remains one of the principal challenges in oncology. [Mol Cancer Ther 2008;7(8):2498 -508]

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Changes in glycolipid expression in human testicular tumor

Cited by 53 publications

References 22 publications

The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

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