Inverse relationship of expression between GM3 and globo-series ganglioside in human renal cell carcinoma.

Renal cell carcinoma (RCC) is highly metastatic. We previously showed that expression of globo-series ganglioside is associated with the metastatic potential of RCC. However, the mechanism of metastasis remains largely unknown, and there is no effective therapy for metastasis. It was recently shown that induction of differentiation of colon cancer cells by brefeldin A was accompanied by an increase of GM3 with a concomitant decrease of neolacto-series gangliosides. To get a clue to a new method of therapy for RCC, we investigated whether the similar changes occur in RCC cells expressing globo-series ganglioside. Growth suppression and an increase of GM3 simultaneous with a decrease of monosialosyl galactosyl globoside, a member of globo-series gangliosides, were observed in human RCC cell line ACHN following brefeldin A treatment. The resultant change of the ganglioside profile is inversely related to the ganglioside pattern associated with the malignant potential of RCC and almost coincided with that representative of RCC cases showing favorable prognoses. It is suggested that the inverse relationship of expression between GM3 and globo-series ganglioside is reflected on the degree of malignancy of RCC, and may be useful as one of the indicators for exploiting treatment methods of RCC.

[1]  C. Ohyama,et al.  Four new human renal cell carcinoma cell lines expressing globo-series gangliosides. , 1999, The Tohoku journal of experimental medicine.

[2]  H. Yamana,et al.  Induction of terminal differentiation and apoptosis in human colonic carcinoma cells by brefeldin A, a drug affecting ganglioside biosynthesis , 1999, FEBS letters.

[3]  K. Handa,et al.  Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation. , 1999, Cancer research.

[4]  T. Ohtsubo,et al.  Inhibition of N‐linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head‐and‐neck carcinoma cells , 1999, International journal of cancer.

[5]  R. Figlin,et al.  Renal cell carcinoma: recent progress and future directions. , 1997, Cancer research.

[6]  C. Ohyama,et al.  Expression of Globo‐series Gangliosides in Human Renal Cell Carcinoma , 1997, Japanese journal of cancer research : Gann.

[7]  S. Hakomori.  Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. , 1996, Cancer research.

[8]  K. Handa,et al.  Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential. , 1996, Cancer research.

[9]  S. Hakomori,et al.  Common tetrasaccharide epitope NeuAc alpha 2-->3Gal beta 1-->3(Neu-Ac alpha 2-->6)GalNAc, presented by different carrier glycosylceramides or O-linked peptides, is recognized by different antibodies and ligands having distinct specificities. , 1994, The Journal of biological chemistry.

[10]  P. Goss,et al.  A phase I study of swainsonine in patients with advanced malignancies. , 1993, Cancer research.

[11]  E. Holmes,et al.  Brefeldin A induced inhibition of de novo globo- and neolacto-series glycolipid core chain biosynthesis in human cells. Evidence for an effect on beta 1-->4galactosyltransferase activity. , 1992, The Journal of biological chemistry.

[12]  C. Ohyama,et al.  Changes in glycolipids in human renal‐cell carcinoma and their clinical significance , 1991, International journal of cancer.

[13]  S. Hakomori,et al.  Glycoconjugate expression during embryogenesis and its biological significance , 1990, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  F. Takaku,et al.  Ganglioside GM3: an acidic membrane component that increases during macrophage-like cell differentiation can induce monocytic differentiation of human myeloid and monocytoid leukemic cell lines HL-60 and U937. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Magnani,et al.  Detection of gangliosides that bind cholera toxin: direct binding of 125I-labeled toxin to thin-layer chromatograms. , 1980, Analytical biochemistry.