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Glycosaminoglycans and syndecan-4 are involved in SDF-1/CXCL12-mediated invasion of human epitheloid carcinoma HeLa cells.

Abstract : BACKGROUND: In addition to their physiologic effects in inflammation and angiogenesis, chemokines are involved in cancer pathology. The CXC-chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 mediates its biological activities through activation of G protein-coupled receptor CXCR4 and binds to glycosaminoglycans (GAGs). METHODS: Using Bio-coat cell migration chambers, specific antagonists, flow cytometry and RNA interference, we evaluate the involvement of heparan sulfate proteoglycans (HSPG) in the SDF-1/CXCL12-induced invasion of human cervix epitheloid carcinoma HeLa cells. RESULTS: The SDF-1/CXCL12-induced cell invasion is dependent on CXCR4. Furthermore, Protein Kinase C delta (PKC delta) and c-jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) are implicated in this event, but not extracellular signal-regulated kinase (ERK) 1/2. Moreover, the invasion of HeLa cells induced by SDF-1/CXCL12 was dependent on matrix metalloproteinase-9 (MMP-9). The pre-incubation of HeLa cells with heparin or with anti-heparan sulfate antibodies or with beta-d-xyloside inhibited SDF-1/CXCL12-mediated cell invasion. Furthermore, the down-regulation of syndecan-4, a heparan sulfate proteoglycan, decreased SDF-1/CXCL12-mediated HeLa cell invasion. CONCLUSION: GAGs, probably on syndecan-4, are involved in SDF-1/CXCL12-mediated cell chemotaxis. GENERAL SIGNIFICANCE: These data suggest that targeting the glycosaminoglycan/chemokine interaction could be a new therapeutic approach for carcinomas in which SDF-1/CXCL12 is involved.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00415321
Contributor : Françoise Baleux <>
Submitted on : Thursday, September 10, 2009 - 2:51:10 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:31 AM

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Severine Brule, Véronique Friand, Angela Sutton, Françoise Baleux, Liliane Gattegno, et al.. Glycosaminoglycans and syndecan-4 are involved in SDF-1/CXCL12-mediated invasion of human epitheloid carcinoma HeLa cells.. Biochimica et Biophysica Acta - Molecular Cell Research, Elsevier, 2009, epub ahead of print. ⟨10.1016/j.bbagen.2009.08.001⟩. ⟨pasteur-00415321⟩

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