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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1761-1767. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-08-3182. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3182v1 107/5/1761    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Burger, J. A. Articles by Kipps, T. J. Search for Related Content PubMed PubMed Citation Articles by Burger, J. A. Articles by Kipps, T. J. Related Collections Neoplasia Reviews in Translational Hematology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEW ARTICLES CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment Jan A. Burger, and Thomas J. Kipps From the Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston; and the Division of Hematology/Oncology, Department of Medicine, University of California, San Diego. Signals from the microenvironment have a profound influence on the maintenance and/or progression of hematopoietic and epithelial cancers. Mesenchymal or marrow-derived stromal cells, which constitute a large proportion of the non-neoplastic cells within the tumor microenvironment, constitutively secrete the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). CXCL12 secretion by stromal cells attracts cancer cells, acting through its cognate receptor, CXCR4, which is expressed by both hematopoietic and nonhematopoietic tumor cells. CXCR4 promotes tumor progression by direct and indirect mechanisms. First, CXCR4 is essential for metastatic spread to organs where CXCL12 is expressed, and thereby allows tumor cells to access cellular niches, such as the marrow, that favor tumor-cell survival and growth. Second, stromal-derived CXCL12 itself can stimulate survival and growth of neoplastic cells in a paracrine fashion. Third, CXCL12 can promote tumor angiogenesis by attracting endothelial cells to the tumor microenvironment. CXCR4 expression is a prognostic marker in various types of cancer, such as acute myelogenous leukemia or breast carcinoma. Promising results in preclinical tumor models indicate that CXCR4 antagonists may have antitumor activity in patients with various malignancies. 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