Biosignals modulated by tumor-associated carbohydrate antigens: novel targets for cancer therapy.
Based on the remodeling of glycosphingolipids on the human tumor cell lines with manipulation of glycosyltransferase genes, roles of sugar moieties in tumor-associated carbohydrate antigens have been analyzed. Two main topics, that is, the roles of ganglioside GD3 in human malignant melanomas and those of GD2 in small cell lung cancer (SCLC) were reported. GD3 enhances tyrosine phosphorylation of two adaptor molecules, p130Cas and paxillin, resulting in the increased cell growth and invasion in melanoma cells. GD2 also enhances the proliferation and invasion of SCLC cells. GD2 also mediates apoptosis with anti-GD2 monoclonal antibodies (mAbs) via dephosphorylation of the focal adhesion kinase. These approaches have promoted further understanding of mechanisms by which gangliosides modulate malignant properties of human cancer, and the results obtained here propose novel targets for cancer therapy.
Furukawa
Koichi
K
Department of Biochemistry II, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan. koichi@med.nagoya-u.ac.jp
Hamamura
Kazunori
K
Aixinjueluo
Wei
W
Furukawa
Keiko
K
D023102:Anoikis / Q000187:drug effects / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005732:Gangliosides / Q000502:physiology*; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D005732:Gangliosides; D006028:Glycosphingolipids; D051419:Paxillin; D014443:Tyrosine; C026226:ganglioside, GD3; C019403:ganglioside, GD2; D051416:Focal Adhesion Protein-Tyrosine Kinases