Prostate Cancer is a leading cause of illness and death among men all over the world, it is considered the third most common cause of death from cancer in men of all ages.
CCR5 (C-C chemokine receptor type 5) and its ligands are of a major interest in prostatic cancer since It has been recently shown that patients with CCR5Δ32 deletion mutation display a high state of resistance to the development of prostate cancer. CCR5 is a G-protein coupled receptor functioning as the receptor for CC chemokines for example CCL3, CCL4 and CCL5 known as RANTES.
Chemokines are small (~8-14kDa), structurally related chemotactic cytokines that regulate cell trafficking. Downstream signals enable the chemokines to regulate cell trafficking. As for cancer diseases chemokines are produced by cancer cells that also possess their chemokine receptors. CCR5 Ligands have been recently suggested to serve as growth/survival factors for androgen dependent cancer diseases.
Recent studies, including one that has been previously conducted in prof. Karin's lab, show that the mechanisms by which chemokines assist tumor development and angiogenesis include autocrine mechanisms in which chemokines produced by tumor cells act on the cell's surface receptors to promote tumor cell proliferation and survival, and paracrine effects, by which chemokines produced by tumor cells attract bone marrow derived (BMDR) cells to support tumor growth and angiogenesis.
Two major types of BMDR cells were highly associated with supporting tumor growth and angiogenesis; CCR2+ tumor associated macrophages (TAMS) and Gr-1+ myeloid derived cells in particular CD11b+/Gr-1+ myeloid cells, that include cells of the granulocytic lineage and the monocytic lineage, immature dendritic cells, and a minor fraction of progenitor populations capable of differentiating into any of the other three subpopulations.
The chemokine receptor that primarily drives the recruitment of Gr-1+ myeloid derived cells to support tumor angiogenesis is still unknown.
