Heparin--a unique stimulator of human colon cancer cells' growth.
The cancer microenvironment and the interactions between cancer and surrounding tissue cells are thought to play a pivotal role in tumor development and progression. Glycosaminoglycans (GAGs)/proteoglycans (PGs) are major constituents of the extracellular matrix, the composition of which may affect various cellular functions. In the present study, the effects of GAGs on the proliferation of HT29, SW1116, and HCT116 human colon cancer cell lines were examined using exogenously added GAGs, an inhibitor of endogenous GAG sulfation and specific glycosidase digestions. Our results demonstrate that colon cancer cell growth was exclusively stimulated by exogenously added heparin and insensitive to endogenous GAGs/PGs production, in a sulfation pattern-related manner. Treatment of the tested cell lines with the FGF-2 neutralizing antibody showed that the stimulatory effect of heparin on the cells' growth was not FGF-2-dependent. Responsiveness of colon cancer cell lines to exogenous heparin/heparan sulfate may play a role in their growth and metastasis.
Chatzinikolaou
Georgia
G
Department of Histology, Division of Morphology, School of Medicine, University of Crete, Heraklion, Greece.
Nikitovic
Dragana
D
Asimakopoulou
Athanasia
A
Tsatsakis
Aristidis
A
Karamanos
Nikos K
NK
Tzanakakis
George N
GN
D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003871:Dermatan Sulfate / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013431:Sulfates / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005343:Fibrinolytic Agents; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D013431:Sulfates