Staphylococcal Superantigen-like 10 Inhibits CXCL12-Induced Human Tumor Cell Migration

Purpose: Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. CXCR4 is the most widely expressed chemokine receptor in many different types of cancer and has been linked to tumor dissemination and poo...

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Published in:Neoplasia (New York, N.Y.) N.Y.), 2009-04, Vol.11 (4), p.333-344
Main Authors: Walenkamp, Annemiek M.E., Boer, Ingrid G.J., Bestebroer, Jovanka, Rozeveld, Dennie, Timmer-Bosscha, Hetty, Hemrika, Wieger, van Strijp, Jos A.G., de Haas, Carla J.C.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Blotting, Western
Cell Line, Tumor
Cell Movement - drug effects
Chemokine CXCL12 - metabolism
Humans
Neoplasms - immunology
Neoplasms - metabolism
Polymerase Chain Reaction
Receptors, CXCR4 - antagonists & inhibitors
Staphylococcus - immunology
Superantigens - pharmacology
Transfection
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Summary:Purpose: Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. CXCR4 is the most widely expressed chemokine receptor in many different types of cancer and has been linked to tumor dissemination and poor prognosis. Several CXCR4 antagonists have been synthesized. A totally novel approach to discover chemokine receptor antagonists is the use of bacteria. Bacteria produce chemokine receptor inhibitors to prevent neutrophil extravasation and migration toward the infection site to escape clearance by innate immune cells. The aim of the current study was to find and identify the mechanism of a bacterial protein that specifically targets CXCR4, a chemokine receptor shared by neutrophils and cancer cells. Experimental Design: Several staphylococcal proteins were screened for their capacity to prevent binding of a function-blocking antibody against CXCR4. Results: Staphylococcal superantigen-like 10 was found to bind CXCR4 expressed on human T acute lymphoblastic leukemia, lymphoma, and cervical carcinoma cell lines. It potently inhibited CXCL12-induced calcium mobilization and cell migration. Conclusions: Staphylococcal superantigen-like 10 is a potential lead in the development of new anticancer compounds preventing metastasis by targeting CXCR4.
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1593/neo.81508