The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer

Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor 48109, USA.
Journal of Biological Chemistry (Impact Factor: 4.6). 03/2008; 283(7):4283-94. DOI: 10.1074/jbc.M707465200
Source: PubMed

ABSTRACT Several reports have recently documented that CXCR7/RDC1 functions as a chemokine receptor for SDF-1/CXCL12, which regulates
a spectrum of normal and pathological processes. In this study, the role of CXCR7/RDC1 in prostate cancer (PCa) was explored.
Staining of high density tissue microarrays demonstrates that the levels of CXCR7/RDC1 expression increase as the tumors become
more aggressive. In vitro and in vivo studies with PCa cell lines suggest that alterations in CXCR7/RDC1 expression are associated with enhanced adhesive and invasive
activities in addition to a survival advantage. In addition, it was observed that CXCR7/RDC1 levels are regulated by CXCR4.
Among the potential downstream targets of CXCR7/RDC1 are CD44 and cadherin-11, which are likely to contribute to the invasiveness
of PCa cells. CXCR7/RDC1 also regulates the expression of the proangiogenic factors interleukin-8 or vascular endothelial
growth factor, which are likely to participate in the regulation of tumor angiogenesis. Finally, we found that signaling by
CXCR7/RDC1 activates AKT pathways. Together, these data demonstrate a role for CXCR7/RDC1 in PCa metastasis and progression
and suggest potential targets for therapeutic intervention.

Download full-text


Available from: Yusuke Shiozawa, Jul 01, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.
    International Journal of Endocrinology 11/2014; 2014:753524. DOI:10.1155/2014/753524 · 1.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Osteosarcoma (OS) is the most frequent primary malignant bone tumour in children and adolescents with a high propensity for lung metastasis. Chemokines and chemokine receptors have been described to have an important role in many malignancies including OS. The aim of this study was to investigate the expression of CXCR7 receptor in OS tissues and its role in the progression of the disease in the lungs.Methods:Immunohistochemistry was used to study CXCR7 expression in primary tumours and metastatic tissues from patients with OS. Its contribution to tumour expansion in the lungs has been also assessed using animal models and synthetic-specific CXCR7 ligands.Results:CXCR7 was expressed on human primary bone tumours and on lung metastases. Its expression was predominantly located on tumour-associated blood vessels. Mice challenged with OS cells and systematically treated with synthetic CXCR7 ligands presented a significant reduction of lung nodules compared with untreated mice.Conclusion:This study shows that CXCR7 has a critical role in OS progression in the lungs, where are expressed CXCR7 ligands, especially CXCL12. Moreover, we highlight that synthetic CXCR7 ligands could represent a powerful therapeutic tool to impede lung OS progression.British Journal of Cancer advance online publication, 3 September 2013; doi:10.1038/bjc.2013.482
    British Journal of Cancer 09/2013; 109(6). DOI:10.1038/bjc.2013.482 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bone metastases are a dismal consequence for different types of solid tumors, such as breast, prostate, lung, and kidney cancer. The mechanisms regulating the interactions among bone, immune system, and tumor cells have been deeply investigated, and many studies are ongoing to define the specific role of the different cells in the bone metastatic process. The affinity of some tumors to growth in bone results from the special microenvironment provided by bone. Moreover, immune system and bone have a bidirectional relationship: bone cells express surface molecules ruling the expansion of hemopoietic stem cells from which all cells of the mammalian immune system derive, and various immunoregulatory cytokines influence the fate of bone cells. The last findings allow to extend the concept of vicious cycle and add T cells as mediators of the tumor growth in bone.
    Clinical and Developmental Immunology 04/2013; 2013:315024. DOI:10.1155/2013/315024 · 2.93 Impact Factor