1. C-C chemokine receptor 5 on stromal cells promotes pulmonary metastasis.
- Author
-
van Deventer HW, O'Connor W Jr, Brickey WJ, Aris RM, Ting JP, and Serody JS
- Subjects
- Animals, Dendritic Cells immunology, Dendritic Cells metabolism, Female, Immunotherapy, Adoptive, Lung Neoplasms immunology, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Melanoma, Experimental immunology, Melanoma, Experimental metabolism, Melanoma, Experimental pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, CCR5 biosynthesis, Receptors, CCR5 deficiency, Stromal Cells metabolism, Lung Neoplasms secondary, Melanoma, Experimental secondary, Receptors, CCR5 physiology
- Abstract
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
- 2005
- Full Text
- View/download PDF