CXCR4 Chemokine Receptor Overview: Biology, Pathology and Applications in Imaging and Therapy


CXCR4 is a member of the chemokine receptor subfamily of seven transmembrane domained, G-protein coupled receptors, whose sole known natural ligand is CXCL12/SDF-1. CXCR4 is an unusual chemokine receptor by virtue of having expanded roles beyond leukocyte recruitment, including fundamental processes such as the development of the hematopoietic, cardiovascular, and nervous systems during embryogenesis. The receptor was first discovered as one of the co-receptors for HIV, and thereafter was also found to be expressed by multiple cancers including breast, prostate, lung, colon and multiple myeloma. A number of recent studies have correlated high levels of CXCR4 expression in cancers with poor prognosis and with resistance to chemotherapy, in part through enhancing interactions between cancers and stroma. A possible role for CXCR4, and chemokine receptors generally, in cancer and metastasis was first suggested in studies of breast cancer, showing that the receptor plays a role in directing metastatic cells to CXCL12-expressing organs. Collectively, the data on CXCR4 in cancer suggest that this receptor increases tumor cell survival and/or growth and/or metastasis, making it a potentially attractive therapeutic target. Due to the role of CXCR4 in HIV, multiple CXCR4 antagonists, although not sufficient for the treatment of HIV, are currently being evaluated and/or used for stem cell mobilization and as anti-tumor therapy. Some of the antagonists were also shown in animal models to be of use in evaluating CXCR4 expression in whole tumors non-invasively by molecular imaging. The research on CXCR4 has been ongoing for the last decade and yielded more than 7400 papers in PubMed as of December 2012. In this issue we tried to collect papers which represent CXCR4 involvement in various fields, from roles under normal conditions, to different pathologies, and finally to molecules targeting CXCR4 for theranostics. The only CXCR4 antagonist which is currently approved for treatment of patients is Mozobil (also known as Plerixafor and AMD3100). This drug was approved by the FDA in December 2008 as an aid for mobilizing hematopoietic stem cells from the bone marrow to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma. The drug approval was given as a combination therapy, with the more traditional stem cell mobilizer granulocyte-colony stimulating factor (GCSF). The role of CXCR4 in hematopoietic stem cell mobilization, and modulation of the receptor and its ligand CXCL12 (SDF-1) were discussed in the review by Ratajczak et al. [1]. The roles of CXCR4 and its ligand CXCL12 in developement are substantial, and are most evident from the fact that knock-out mice for either protein are lethal. We chose to bring an example of a less known role of CXCR4, which is its involvment in pancreatic developement. Recent findings in this area are reviewed by Katsumoto et al. in this issue [2]. The primary pathology in which CXCR4 was Ivyspring

DOI: 10.7150/thno.5760

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@inproceedings{Jacobson2013CXCR4CR, title={CXCR4 Chemokine Receptor Overview: Biology, Pathology and Applications in Imaging and Therapy}, author={Orit Jacobson and Ido Dov Weiss}, booktitle={Theranostics}, year={2013} }