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BioMed Research International
Volume 2015 (2015), Article ID 195828, 9 pages
http://dx.doi.org/10.1155/2015/195828
Research Article

Construction of a CXCL12-KDEL Fusion Gene to Inhibit Head and Neck Squamous Cell Carcinoma Metastasis by Intracellular Sequestration of CXCR4

Department of Maxillofacial and ENT, National Cancer Clinical Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China

Received 26 June 2014; Revised 18 August 2014; Accepted 19 August 2014

Academic Editor: Shiwu Zhang

Copyright © 2015 Wenchao Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and its specific receptor CXCR4 plays an important role in oral cancer metastasis. High expression of CXCR4 may help oral squamous cancer cells invade local tissues and metastasize to lymph nodes. No obvious association was observed between CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis may only be related to CXCR4 expression on the tumor cell membrane. KDEL can be retained by receptors on the surface of the intracellular endoplasmic reticulum (ER) and also be called an ER retention signal sequence. So we adopted the KDEL sequence in this study to generate a CXCL12-KDEL fusion protein in combination with a traceable E-tag label. As such, CXCL12 was retained in the ER. Specific receptor CXCR4 binds to the CXCL12-KDEL, was also retained in the ER, and was thus prevented from reaching the oral squamous cancer cell surface. We reduced the cell surface level of CXCR4 and called the technique “intracellular sequestration.” By this way, we have finished blocking of CXCL12-CXCR4 biological axis and inhibiting lymph node metastasis of oral carcinoma.