Alteration of tumor phenotypes of B16 melanoma after genetic remodeling of the ganglioside profile.

Tsurifune, Takahito; Ito, Tetsuya; Li, X J; Yamashiro, Susumu; Okada, Masahiko; Kanematsu, Takashi; Shiku, Hiroshi; Furukawa, Kiyonori

doi:10.3892/ijo.17.1.159

Cited by 6 publications

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“…In particular, tandem‐repeated sialic acid‐structures such as those in GD3 and GD2 enhanced the malignant properties of cancer cells, such as cell proliferation, cell invasion and migration, cell adhesion, and metastasis . In contrast, monosialyl gangliosides, such as GM1, GM3, and GM2 often suppress malignant properties of various cancer cells . Therefore, GD3 synthase is a key enzyme determining cell phenotypes based on the expression patterns of gangliosides, as shown in Figure .…”

Section: Glycosphingolipids As Functional Molecules On the Cell Surfacementioning

confidence: 99%

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New era of research on cancer‐associated glycosphingolipids

et al. 2019

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Cancer‐associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors. Recent progress in the analysis of their implications in the malignant properties of cancer cells revealed that cancer‐associated glycosphingolipids are not only tumor markers, but also functional molecules regulating various signals introduced by membrane microdomains, lipid rafts. In particular, a novel approach, enzyme‐mediated activation of radical sources combined with mass spectrometry, has enabled us to clarify the mechanisms by which cancer‐associated glycosphingolipids regulate cell signals based on the interaction with membrane molecules and formation of molecular complexes on the cell surface. Novel findings obtained from these approaches are now providing us with insights into the development of new anticancer therapies targeting membrane molecular complexes consisting of cancer‐associated glycolipids and their associated membrane molecules. Thus, a new era of cancer‐associated glycosphingolipids has now begun.

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Section: Glycosphingolipids As Functional Molecules On the Cell Surfacementioning

confidence: 99%

“…[15][16][17] In contrast, monosialyl gangliosides, such as GM1, GM3, and GM2 often suppress malignant properties of various cancer cells. [18][19][20] Therefore, GD3 synthase is a key enzyme determining cell phenotypes based on the expression patterns of gangliosides, as shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

New era of research on cancer‐associated glycosphingolipids

et al. 2019

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“…However, no changes in the expression levels of various adhesion molecules, including integrin α5β1, could be detected after introduction of the GM 2 /GD 2 synthase gene. Adhesion to fibronectin‐coated plates revealed marked delay in GM 2 + transfectants; and phosphorylation levels of FAK, an important kinase downstream of the integrins,31, 32 was also markedly reduced in transfectants. These results indicated that carbohydrate changes in gangliosides modulated the cellular signals mediated via integrin α5β1/fibronectin.…”

Section: Discussionmentioning

confidence: 99%

Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM₂/GD₂ synthase gene

Chen

Fukumoto

Furukawa

et al. 2002

Intl Journal of Cancer

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Ganglioside functions in tumor metastasis were analyzed by carbohydrate remodeling of a mouse Lewis lung cancer (subline P29) by introducing ␤1,4GalNAc-T cDNA. Although P29 was originally a low-metastatic subline in the s.c. injection system, it showed high potential in lung metastasis when i.v.-injected via the tail vein. Two lines of GM 2 ؉ transfectants showed markedly reduced metastatic potential to the lung compared to 2 control lines. However, cell proliferation rates and expression levels of various cell adhesion molecules, e.g., integrin family members, SLe x and CD44, were essentially unchanged after transfection of the cDNA. Gangliosides have been considered to play important roles in cell-cell and cell-extracellular matrix recognition and in the modulation of cellular signals on the cell-surface membrane. 1 In particular, gangliosides have been thought to be involved in cell attachment in the case of melanomas, 2-4 neuroblastomas, 3,5,6 gliomas, 7 osteosarcomas 8 and lymphosarcomas. 9 Tumor metastasis results from the successful completion of a series of processes, i.e., detachment and movement of tumor cells from primary sites, invasion into the blood vessel, migration in the bloodstream, adhesion to a vessel wall of a distant organ, invasion across the vessel wall to a secondary site and proliferation to form micro-and macrometastases. 10 One of the most likely situations in which gangliosides are involved in cancer metastasis appears to be adhesion to blood vessels and invasion across vessel walls.Among cancer-associated gangliosides, GM 2 (ganglioside nomenclature is based on that of Svennerholm 10a ) is widely expressed in various epithelial cancer cell types, 11-13 while it is hard to detect GM 2 in normal tissues. In melanoma cells and tissues, GD 3 is commonly and strongly expressed at all stages of the disease 14 -16 and GM 2 /GD 2 appears mainly when the tumors proceed and become more metastatic. 17,18 This is based on novel expression of the GM 2 /GD 2 synthase gene at the advanced phase of the tumor. To clarify the genetic mechanisms for these phenotypic changes of tumors such as melanomas, we isolated the cDNA of ganglioside synthase genes 19 -21 and studied the expression of those glycosyltransferase genes in various tumors. 13,22,23 From this background, we expected that transfection of the GM 2 /GD 2 synthase gene might induce increased metastasis of tumors.To investigate the roles of gangliosides in cancer metastasis in vivo, we used a mouse lung cancer line, Lewis, which has been employed previously in in vivo cancer metastasis studies. 24 P29 is a low-metastatic subline of Lewis lung cancer in the experimental system of s.c. inoculation. 24,25 However, it showed high metastatic potential to the lung when cells were inoculated into the tail vein, suggesting its high adherent activity to endothelia of lung blood vessels.We established GM 2 /GD 2 synthase gene transfectants of P29 and analyzed their metastatic properties; these cells express high levels of GM 2 . Surprisingly, GM 2 -e...

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“…Further studies should also elucidate the growth-regulatory effects of gangliosides on in vitro coculture of melanoma with stromal cells such as macrophages, ®broblasts, and especially endothelial cells. In addition to the exogenous administration of gangliosides, the genetic remodeling of the ganglioside pro®le in melanoma may alter its growth modality; transfection of sialidase cDNA into murine B16 melanoma decreased intracellular GM3 expression and pulmonary metastasis (Tokuyama et al, 1997), and transfection of GM2/GD2 synthase cDNA into B16 induced GM2 expression and reduced cexpression and in vitro and in vivo growth rate (Tsurifune et al, 2000). The transfection of antisense vector against GD3 synthase reduced GD3 expression and in vivo growth rate of rat F-11 neural tumor cells (Zeng et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Gangliosides GD1b, GT1b, and GQ1b Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production: the Inhibition of Adenylate Cyclase11The nomenclature for gangliosides used in this paper follows the system ofSvennerholm (1963).

Kanda

Nakai

Watanabe

2001

Journal of Investigative Dermatology

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We studied the effects of various gangliosides on in vitro growth of human metastatic melanoma WM266-4. GD1b, GT1b, and GQ1b inhibited 3H-thymidine uptake and growth rate of WM266-4 whereas the other gangliosides were ineffective. The growth inhibition by GD1b, GT1b, and GQ1b was counteracted by interleukin-8 but not by the other growth factors. The growth inhibition by gangliosides was not detected in the presence of anti-interleukin-8 antibody. GD1b, GT1b, and GQ1b reduced the constitutive interleukin-8 secretion and mRNA levels in WM266-4. Transient transfection showed that GD1b, GT1b, and GQ1b inhibited the constitutive chloramphenicol acetyltransferase expression driven by interleukin-8 promoter in WM266-4. Transfection with a series of 5'-deleted mutants demonstrated that the sequences between -98 and -62 bp on interleukin-8 promoter may be involved in the transcriptional repression by these gangliosides. Cyclic AMP analog dibutyryl cAMP counteracted GD1b, GT1b, and GQ1b-induced inhibition of interleukin-8 production at the levels of protein secretion, mRNA expression, and promoter activity. GD1b, GT1b, and GQ1b reduced cAMP level and protein kinase A activity in WM266-4. These gangliosides suppressed adenylate cyclase activity without altering that of cyclic nucleotide phosphodiesterase in WM266-4. The data indicate that GD1b, GT1b, and GQ1b may suppress the growth of melanoma by inhibiting interleukin-8 production via the inhibition of adenylate cyclase.

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Alteration of tumor phenotypes of B16 melanoma after genetic remodeling of the ganglioside profile.

Cited by 6 publications

References 0 publications

New era of research on cancer‐associated glycosphingolipids

New era of research on cancer‐associated glycosphingolipids

Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM₂/GD₂ synthase gene

Gangliosides GD1b, GT1b, and GQ1b Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production: the Inhibition of Adenylate Cyclase11The nomenclature for gangliosides used in this paper follows the system ofSvennerholm (1963).

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Alteration of tumor phenotypes of B16 melanoma after genetic remodeling of the ganglioside profile.

Cited by 6 publications

References 0 publications

New era of research on cancer‐associated glycosphingolipids

New era of research on cancer‐associated glycosphingolipids

Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene

Gangliosides GD1b, GT1b, and GQ1b Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production: the Inhibition of Adenylate Cyclase11The nomenclature for gangliosides used in this paper follows the system ofSvennerholm (1963).

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Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM₂/GD₂ synthase gene