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Estrogen Disrupts Chemokine-Mediated Chemokine Release from Mammary Cells: Implications for the Interplay between Estrogen and IP-10 in the Regulation of Mammary Tumor Formation

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Abstract

Chemokines are pro-inflammatory cytokines that function to attract immune cells to the sites of tissue inflammation, injury or infection. We have formulated the hypothesis that release of one chemokine can serve, in a local paracrine or endocrine fashion, to induce the release of other chemokines from neighboring mammary cells. We set out to investigate whether specific chemokines could promote the release of other chemokine members from mammary cells, and whether estrogen could serve to disrupt the release of these chemokines from mammary cells. We found that treatment with the chemokine IP-10 resulted in significant increases in the amount of MIP-1α and MCP-1/JE released from murine mammary cells. Estrogen co-treatment significantly blocked the ability of IP-10 to trigger the release of MIP-1α and MCP-1/JE. Suppressive effects of estrogen were reversed upon co-treatment with 4-hydroxytamoxifen. Estrogen treatment significantly decreased expression of proteins corresponding to the chemokine receptors CXCR3 and CCR5 on mammary cells. Exposure of female mice to IP-10 in vivo significantly decreased the ability of estrogen to support the growth of CCL-51-based tumors in mammary tissue. Our results suggest that exposure of mammary tissue to estrogen may decrease the release of local chemokines from mammary cells, potentially increasing the risk of tumor growth through decreased immune surveillance. Ongoing studies are investigating the possible mechanisms through which IP-10 stimulates the release of chemokines from mammary cells, and how the action of IP-10 may serve to decrease mammary tumor formation.

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Authors and Affiliations

  1. Department of Biology, Canisius College, Buffalo, NY, USA

    S.M. Aronica, P. Fanti, K. Kaminskaya, K. Gibbs, L. Raiber, M. Nazareth, R. Bucelli, M. Mineo, K. Grzybek, M. Kumin, K. Poppenberg, C. Schwach & K. Janis

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  1. S.M. Aronica
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  2. P. Fanti
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  3. K. Kaminskaya
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  4. K. Gibbs
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  5. L. Raiber
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  6. M. Nazareth
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  7. R. Bucelli
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  8. M. Mineo
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  9. K. Grzybek
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  10. M. Kumin
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  11. K. Poppenberg
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  12. C. Schwach
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  13. K. Janis
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Aronica, S., Fanti, P., Kaminskaya, K. et al. Estrogen Disrupts Chemokine-Mediated Chemokine Release from Mammary Cells: Implications for the Interplay between Estrogen and IP-10 in the Regulation of Mammary Tumor Formation. Breast Cancer Res Treat 84, 235–245 (2004). https://doi.org/10.1023/B:BREA.0000019961.59306.f6

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  • DOI: https://doi.org/10.1023/B:BREA.0000019961.59306.f6

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