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

Abstract
Ganglioside functions in tumor metastasis were analyzed by carbohydrate remodeling of a mouse Lewis lung cancer (subline P29) by introducing beta1,4GalNAc-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. Then, cell adhesion to fibronectin-coated dishes was examined, showing that GM(2) (+) transfectants attached to the plates much more slowly than controls, suggesting functional modulation of integrins with newly expressed GM(2). Phosphorylation of the FAK located at downstream of integrin molecules was markedly reduced in GM(2)(+) transfectants, suggesting that GM(2) suppressed cell adhesion signals via fibronectin-integrin interaction.
AuthorsHo-Hsiang Chen, Satoshi Fukumoto, Keiko Furukawa, Akimasa Nakao, Seiji Akiyama, Takeshi Urano, Koichi Furukawa
JournalInternational journal of cancer (Int J Cancer) Vol. 103 Issue 2 Pg. 169-76 (Jan 10 2003) ISSN: 0020-7136 [Print] United States
PMID12455030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2002 Wiley-Liss, Inc.
Chemical References
  • DNA, Complementary
  • Gangliosides
  • Integrins
  • Vitronectin
  • G(M2) Ganglioside
  • Tyrosine
  • ganglioside, GD2
  • N-Acetylgalactosaminyltransferases
  • (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, mouse
Topics
  • Animals
  • Carcinoma, Lewis Lung (metabolism, prevention & control, secondary)
  • Cell Membrane (metabolism)
  • DNA, Complementary
  • Female
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • G(M2) Ganglioside (metabolism)
  • Gangliosides (metabolism)
  • Integrins (metabolism)
  • Lung Neoplasms (metabolism, prevention & control, secondary)
  • Mice
  • Mice, Inbred C57BL
  • N-Acetylgalactosaminyltransferases (genetics, metabolism)
  • Neoplasm Transplantation
  • Phosphorylation
  • Protein-Tyrosine Kinases (metabolism)
  • Skin Neoplasms (metabolism, pathology, prevention & control)
  • Transfection
  • Tumor Cells, Cultured
  • Tyrosine (metabolism)
  • Vitronectin (metabolism)

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