CC chemokine receptor 5 on stromal cells promotes pulmonary metastasis

HW van Deventer, W O'Connor Jr, WJ Brickey, RM Aris… - Cancer research, 2005 - AACR
HW van Deventer, W O'Connor Jr, WJ Brickey, RM Aris, JPY Ting, JS Serody
Cancer research, 2005AACR
We have shown that mice that express the CC 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× 106 B16-F10 melanoma cells. These results …
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 × 106 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.
AACR