TY - JOUR
T1 - Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer
T2 - A basis for tumor-promoting interactions
AU - Soria, Gali
AU - Yaal-Hahoshen, Neora
AU - Azenshtein, Elina
AU - Shina, Sima
AU - Leider-Trejo, Leonor
AU - Ryvo, Larisa
AU - Cohen-Hillel, Efrat
AU - Shtabsky, Alex
AU - Ehrlich, Marcelo
AU - Meshel, Tsipi
AU - Keydar, Iafa
AU - Ben-Baruch, Adit
N1 - Funding Information:
The authors thank Ms. F.R. Warshaw-Dadon (Jerusalem, Israel) for editorial advice. The study was supported by: The Israel Academy of Sciences and Humanities; The Israel Cancer Association through the donation from Ms. Beatrice Brown & Friends in memory of Arleen Solarsh; The Ela Kodesz Institute for Research on Cancer Development and Prevention; The Oncology Memorial (Fund), Tel-Aviv, Israel; The Simko Chair for Breast Cancer Research; The Federico Foundation.
PY - 2008/10
Y1 - 2008/10
N2 - The chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast malignancy. In the present study, we asked if the two chemokines are jointly expressed in clinical samples of breast cancer patients, and do they interact in breast tumor cells. We found that RANTES and MCP-1 were expressed by breast tumor cells in primary tumors of Ductal Carcinoma In Situ and of Invasive Ductal Carcinoma, but minimally in normal breast epithelial duct cells. The chemokines were also detected in metastases and pleural effusions. Novel findings showed that co-expression of RANTES and MCP-1 in the same tumor was associated with more advanced stages of disease, suggesting that breast tumors "benefit" from interactions between the two chemokines. Accordingly, MCP-1 significantly promoted the release of RANTES from endogenous pre-made vesicles, in an active process that depended on calcium from intracellular and extracellular sources, and on intracellular transport of RANTES towards exocytosis. Our findings show a chemokine-triggered release of stored pro-malignancy chemokine from breast tumor cells. These observations support a major tumor-promoting role for co-expression of the chemokines in breast malignancy, and agree with the significant association of joint RANTES and MCP-1 expression with advanced stages of breast cancer.
AB - The chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast malignancy. In the present study, we asked if the two chemokines are jointly expressed in clinical samples of breast cancer patients, and do they interact in breast tumor cells. We found that RANTES and MCP-1 were expressed by breast tumor cells in primary tumors of Ductal Carcinoma In Situ and of Invasive Ductal Carcinoma, but minimally in normal breast epithelial duct cells. The chemokines were also detected in metastases and pleural effusions. Novel findings showed that co-expression of RANTES and MCP-1 in the same tumor was associated with more advanced stages of disease, suggesting that breast tumors "benefit" from interactions between the two chemokines. Accordingly, MCP-1 significantly promoted the release of RANTES from endogenous pre-made vesicles, in an active process that depended on calcium from intracellular and extracellular sources, and on intracellular transport of RANTES towards exocytosis. Our findings show a chemokine-triggered release of stored pro-malignancy chemokine from breast tumor cells. These observations support a major tumor-promoting role for co-expression of the chemokines in breast malignancy, and agree with the significant association of joint RANTES and MCP-1 expression with advanced stages of breast cancer.
KW - Breast cancer
KW - Ductal Carcinoma In Situ
KW - Invasive Ductal Carcinoma
KW - MCP-1
KW - RANTES
UR - http://www.scopus.com/inward/record.url?scp=52949094598&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2008.08.002
DO - 10.1016/j.cyto.2008.08.002
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C2 - 18790652
AN - SCOPUS:52949094598
SN - 1043-4666
VL - 44
SP - 191
EP - 200
JO - Cytokine
JF - Cytokine
IS - 1
ER -
