CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature.
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.
Miao
Zhenhua
Z
ChemoCentryx, Inc., Mountain View, CA 94043, USA.
Luker
Kathryn E
KE
Summers
Bretton C
BC
Berahovich
Rob
R
Bhojani
Mahaveer S
MS
Rehemtulla
Alnawaz
A
Kleer
Celina G
CG
Essner
Jeffrey J
JJ
Nasevicius
Aidas
A
Luker
Gary D
GD
Howard
Maureen C
MC
Schall
Thomas J
TJ
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics; D054387:Receptors, CXCR / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
C501896:ACKR3 protein, human; D012334:RNA, Neoplasm; D054387:Receptors, CXCR; D029961:Zebrafish Proteins