Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: A basis for tumor-promoting interactions

Gali Soria, Neora Yaal-Hahoshen, Elina Azenshtein, Sima Shina, Leonor Leider-Trejo, Larisa Ryvo, Efrat Cohen-Hillel, Alex Shtabsky, Marcelo Ehrlich, Tsipi Meshel, Iafa Keydar, Adit Ben-Baruch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalCytokine
Volume44
Issue number1
DOIs
StatePublished - Oct 2008

Funding

FundersFunder number
Ela Kodesz Institute for Research on Cancer Development and Prevention
Tel-Aviv
Israel Academy of Sciences and Humanities
Israel Cancer Association

    Keywords

    • Breast cancer
    • Ductal Carcinoma In Situ
    • Invasive Ductal Carcinoma
    • MCP-1
    • RANTES

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