Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells

Jun Yin, Ayako Hashimoto, Mineko Izawa, Keiko Miyazaki, Guoyun Chen, Hiromu Takematsu, Yasunori Kozutsumi, Akemi Suzuki, Kimio Furuhata, Feng Leng Cheng, Chun Hung Lin, Chihiro Sato, Ken Kitajima, Reiji Kannagi

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Tumor hypoxia figures heavily in malignant progression by altering the intracellular glucose metabolism and inducing angiogenic factor production, thus, selecting and expanding more aggressive cancer cell clones. Little is known, however, regarding hypoxia-induced antigenic changes in cancers. We investigated the expression of N-glycolyl sialic acid (NeuGc)-GM2, a cancer-associated ganglioside containing non-human sialic acid, NeuGc, in human cancers. Cancer tissues prepared from patients with colon cancers frequently expressed NeuGc-GM2, whereas it was virtually absent in nonmalignant colonic epithelia. Studies on cultured cancer cells indicated that the non-human sialic acid was incorporated from culture medium. Hypoxic culture markedly induced mRNA for a sialic acid transporter, sialin, and this accompanied enhanced incorporation of NeuGc as well as N-acetyl sialic acid. Transfection of cells with sialin gene conferred accelerated sialic acid transport and induced cell surface expression of NeuGc-GM2. We propose that the preferential expression of NeuGc-GM2 in cancers is closely associated with tumor hypoxia. Hypoxic culture of tumor cells induces expression of the sialic acid transporter, and enhances the incorporation of non-human sialic acid from the external milieu. A consequence of this is the acquisition of cancer-associated cell surface gangliosides, typically GM2, containing non-human sialic acid (NeuGc), which is not endogenously synthesized through CMP-N-acetyl sialic acid hydroxylase because humans lack the gene for the synthetic enzyme. As hypoxia is associated with diminished response to radiotherapy and chemotherapy, NeuGc-GM2 is a potential therapeutic target for hypoxic cancer cells.

Original languageEnglish (US)
Pages (from-to)2937-2945
Number of pages9
JournalCancer Research
Volume66
Issue number6
DOIs
StatePublished - Mar 15 2006

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Gangliosides
N-Acetylneuraminic Acid
Neoplasms
G(M2) Ganglioside
sialic acid transport proteins
Synthetic Genes
Cytidine Monophosphate
Angiogenesis Inducing Agents
Mixed Function Oxygenases
Colonic Neoplasms
Transfection
Culture Media
Cultured Cells
Radiotherapy
Epithelium
Clone Cells
Cell Culture Techniques
GM2 N-glycolylneuraminic acid ganglioside
Glucose
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells. / Yin, Jun; Hashimoto, Ayako; Izawa, Mineko; Miyazaki, Keiko; Chen, Guoyun; Takematsu, Hiromu; Kozutsumi, Yasunori; Suzuki, Akemi; Furuhata, Kimio; Cheng, Feng Leng; Lin, Chun Hung; Sato, Chihiro; Kitajima, Ken; Kannagi, Reiji.

In: Cancer Research, Vol. 66, No. 6, 15.03.2006, p. 2937-2945.

Research output: Contribution to journalArticle

Yin, J, Hashimoto, A, Izawa, M, Miyazaki, K, Chen, G, Takematsu, H, Kozutsumi, Y, Suzuki, A, Furuhata, K, Cheng, FL, Lin, CH, Sato, C, Kitajima, K & Kannagi, R 2006, 'Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells', Cancer Research, vol. 66, no. 6, pp. 2937-2945. https://doi.org/10.1158/0008-5472.CAN-05-2615
Yin, Jun ; Hashimoto, Ayako ; Izawa, Mineko ; Miyazaki, Keiko ; Chen, Guoyun ; Takematsu, Hiromu ; Kozutsumi, Yasunori ; Suzuki, Akemi ; Furuhata, Kimio ; Cheng, Feng Leng ; Lin, Chun Hung ; Sato, Chihiro ; Kitajima, Ken ; Kannagi, Reiji. / Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells. In: Cancer Research. 2006 ; Vol. 66, No. 6. pp. 2937-2945.
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abstract = "Tumor hypoxia figures heavily in malignant progression by altering the intracellular glucose metabolism and inducing angiogenic factor production, thus, selecting and expanding more aggressive cancer cell clones. Little is known, however, regarding hypoxia-induced antigenic changes in cancers. We investigated the expression of N-glycolyl sialic acid (NeuGc)-GM2, a cancer-associated ganglioside containing non-human sialic acid, NeuGc, in human cancers. Cancer tissues prepared from patients with colon cancers frequently expressed NeuGc-GM2, whereas it was virtually absent in nonmalignant colonic epithelia. Studies on cultured cancer cells indicated that the non-human sialic acid was incorporated from culture medium. Hypoxic culture markedly induced mRNA for a sialic acid transporter, sialin, and this accompanied enhanced incorporation of NeuGc as well as N-acetyl sialic acid. Transfection of cells with sialin gene conferred accelerated sialic acid transport and induced cell surface expression of NeuGc-GM2. We propose that the preferential expression of NeuGc-GM2 in cancers is closely associated with tumor hypoxia. Hypoxic culture of tumor cells induces expression of the sialic acid transporter, and enhances the incorporation of non-human sialic acid from the external milieu. A consequence of this is the acquisition of cancer-associated cell surface gangliosides, typically GM2, containing non-human sialic acid (NeuGc), which is not endogenously synthesized through CMP-N-acetyl sialic acid hydroxylase because humans lack the gene for the synthetic enzyme. As hypoxia is associated with diminished response to radiotherapy and chemotherapy, NeuGc-GM2 is a potential therapeutic target for hypoxic cancer cells.",
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T1 - Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells

AU - Yin, Jun

AU - Hashimoto, Ayako

AU - Izawa, Mineko

AU - Miyazaki, Keiko

AU - Chen, Guoyun

AU - Takematsu, Hiromu

AU - Kozutsumi, Yasunori

AU - Suzuki, Akemi

AU - Furuhata, Kimio

AU - Cheng, Feng Leng

AU - Lin, Chun Hung

AU - Sato, Chihiro

AU - Kitajima, Ken

AU - Kannagi, Reiji

PY - 2006/3/15

Y1 - 2006/3/15

N2 - Tumor hypoxia figures heavily in malignant progression by altering the intracellular glucose metabolism and inducing angiogenic factor production, thus, selecting and expanding more aggressive cancer cell clones. Little is known, however, regarding hypoxia-induced antigenic changes in cancers. We investigated the expression of N-glycolyl sialic acid (NeuGc)-GM2, a cancer-associated ganglioside containing non-human sialic acid, NeuGc, in human cancers. Cancer tissues prepared from patients with colon cancers frequently expressed NeuGc-GM2, whereas it was virtually absent in nonmalignant colonic epithelia. Studies on cultured cancer cells indicated that the non-human sialic acid was incorporated from culture medium. Hypoxic culture markedly induced mRNA for a sialic acid transporter, sialin, and this accompanied enhanced incorporation of NeuGc as well as N-acetyl sialic acid. Transfection of cells with sialin gene conferred accelerated sialic acid transport and induced cell surface expression of NeuGc-GM2. We propose that the preferential expression of NeuGc-GM2 in cancers is closely associated with tumor hypoxia. Hypoxic culture of tumor cells induces expression of the sialic acid transporter, and enhances the incorporation of non-human sialic acid from the external milieu. A consequence of this is the acquisition of cancer-associated cell surface gangliosides, typically GM2, containing non-human sialic acid (NeuGc), which is not endogenously synthesized through CMP-N-acetyl sialic acid hydroxylase because humans lack the gene for the synthetic enzyme. As hypoxia is associated with diminished response to radiotherapy and chemotherapy, NeuGc-GM2 is a potential therapeutic target for hypoxic cancer cells.

AB - Tumor hypoxia figures heavily in malignant progression by altering the intracellular glucose metabolism and inducing angiogenic factor production, thus, selecting and expanding more aggressive cancer cell clones. Little is known, however, regarding hypoxia-induced antigenic changes in cancers. We investigated the expression of N-glycolyl sialic acid (NeuGc)-GM2, a cancer-associated ganglioside containing non-human sialic acid, NeuGc, in human cancers. Cancer tissues prepared from patients with colon cancers frequently expressed NeuGc-GM2, whereas it was virtually absent in nonmalignant colonic epithelia. Studies on cultured cancer cells indicated that the non-human sialic acid was incorporated from culture medium. Hypoxic culture markedly induced mRNA for a sialic acid transporter, sialin, and this accompanied enhanced incorporation of NeuGc as well as N-acetyl sialic acid. Transfection of cells with sialin gene conferred accelerated sialic acid transport and induced cell surface expression of NeuGc-GM2. We propose that the preferential expression of NeuGc-GM2 in cancers is closely associated with tumor hypoxia. Hypoxic culture of tumor cells induces expression of the sialic acid transporter, and enhances the incorporation of non-human sialic acid from the external milieu. A consequence of this is the acquisition of cancer-associated cell surface gangliosides, typically GM2, containing non-human sialic acid (NeuGc), which is not endogenously synthesized through CMP-N-acetyl sialic acid hydroxylase because humans lack the gene for the synthetic enzyme. As hypoxia is associated with diminished response to radiotherapy and chemotherapy, NeuGc-GM2 is a potential therapeutic target for hypoxic cancer cells.

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