CCR1 and CXCR4 expression was observed on multiple myeloma cells (55). The CCR1 and CXCR4 ligands, CCL3 and CXCL12, were expressed at high levels in the bone marrow of patients with multiple myeloma, suggesting that CCR1 and CXCR4 expressed on multiple myeloma cells may mediate their migration to and retention in the bone marrow.
CCR1 was the only chemokine receptor found in hepatitis C-induced hepatocellular carcinoma (56). CCL3 is also expressed and may interact in an autocrine fashion with CCR1 to promote the growth and survival of hepatoma cells. CCR1 and CCL3 were also abundantly expressed in N-nitrosodiethylamine-induced hepatocellular carcinoma tissues and hepatitis B virus surface antigen transgenic mice. In both CCR1-/- and CCL3-/- mice treated with N-nitrosodiethylamine, the number and size of tumor foci were reduced compared with tumor foci in wild-type mice treated with the carcinogen. In contrast, tumor incidence was higher in the knockout mice. Both tumor angiogenesis and the number of intratumoral Kupffer cells, a source of growth factors and matrix metalloproteinases (MMPs), were diminished in N-nitroso-diethylamine-treated CCR1-/- and CCL3-/- mice. MMPs are proteolytic enzymes implicated in metastatic invasion of the extracellular matrix. Expression of MMP-9 and MMP-13 was augmented in the livers of wild-type mice treated with N-nitrosodiethylamine, but MMP-9 gene induction by carcinogen was reduced in CCR1-/- and CCL3-/- mice.
Was this article helpful?