Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment. | ||||||||
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C-C chemokine receptor 5 on stromal cells promotes pulmonary metastasis.van Deventer HW, O'Connor W, Brickey WJ, Aris RM, Ting JP, Serody JS Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Room 3009, Old Clinic Building, NC 27599, USA. hvand@med.unc.edu We have shown that mice that express the C-C chemokine receptor 5 (CCR5) have enhanced local tumor growth and an impaired response to vaccine therapy compared with CCR5 knockout (CCR5(-/-)) mice. Here, we extend these observations to evaluate the function of CCR5 in pulmonary metastasis and the mechanism underlying the diminished tumor growth in CCR5(-/-) mice. Lung metastases were counted in wild-type (WT) and CCR5(-/-) mice following the injection of 1 x 10(6) B16-F10 melanoma cells. These results were compared with those from syngeneic bone marrow chimeric mice formed by the transfer of WT bone marrow into irradiated CCR5(-/-) and CCR5(-/-) marrow into irradiated WT mice. Intact CCR5(-/-) mice developed fewer metastases than WT mice (40.2 versus 70.6; P < 0.05). Bone marrow chimeras formed by the transfer of WT bone marrow into CCR5(-/-) hosts had fewer metastases than WT hosts injected with knockout marrow (46.6 versus 98.6; P < 0.01). Adoptive transfer of CCR5-expressing leukocytes also failed to promote metastasis in CCR5(-/-) mice. However, the i.v. transfer of WT pulmonary stromal cells into CCR5(-/-) mice increased the number of metastases compared with transfer of CCR5(-/-) stromal cells (102.8 versus 26.0; P < 0.05). These results show for the first time that CCR5 expression on stromal and not hematopoietic cells contributes to tumor metastasis. Therefore, recently developed CCR5 inhibitors may have a novel benefit in cancer therapy. Published 18 April 2005 in Cancer Res, 65(8): 3374-9.
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