ZFIN ID: ZDB-PUB-071001-17
CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature
Miao, Z., Luker, K.E., Summers, B.C., Berahovich, R., Bhojani, M.S., Rehemtulla, A., Kleer, C.G., Essner, J.J., Nasevicius, A., Luker, G.D., Howard, M.C., and Schall, T.J.
Date: 2007
Source: Proceedings of the National Academy of Sciences of the United States of America   104(40): 15735-15740 (Journal)
Registered Authors: Essner, Jeffrey, Nasevicius, Aidas
Keywords: angiogenesis, cancer, chemokine
MeSH Terms:
  • Animals
  • Breast Neoplasms/blood supply
  • Breast Neoplasms/pathology*
  • Cell Division
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms/blood supply
  • Lung Neoplasms/pathology*
  • Mice
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/pathology
  • RNA Interference
  • RNA, Neoplasm/genetics
  • Receptors, CXCR/genetics*
  • Receptors, CXCR/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
PubMed: 17898181 Full text @ Proc. Natl. Acad. Sci. USA
FIGURES
ABSTRACT
Chemokines and chemokine receptors have been posited to have important roles in several common malignancies, including breast and lung cancer. Here, we demonstrate that CXCR7 (RDC1, CCX-CKR2), recently deorphanized as a chemokine receptor that binds chemokines CXCL11 and CXCL12, can regulate these two common malignancies. Using a combination of overexpression and RNA interference, we establish that CXCR7 promotes growth of tumors formed from breast and lung cancer cells and enhances experimental lung metastases in immunodeficient as well as immunocompetent mouse models of cancer. These effects did not depend on expression of the related receptor CXCR4. Furthermore, immunohistochemistry of primary human tumor tissue demonstrates extensive CXCR7 expression in human breast and lung cancers, where it is highly expressed on a majority of tumor-associated blood vessels and malignant cells but not expressed on normal vasculature. In addition, a critical role for CXCR7 in vascular formation and angiogenesis during development is demonstrated by using morpholino-mediated knockdown of CXCR7 in zebrafish. Taken together, these data suggest that CXCR7 has key functions in promoting tumor development and progression.
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