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

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-1alpha 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-1alpha 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.

Primary Human Mammary Epithelial Cells Endocytose HIV-1 and Facilitate Viral Infection of CD4 + T Lymphocytes

“…A previous HIV-1 infectivity study using primary human MEC also reported CD4 mRNA transcripts by use of PCR, as well as "faint" expression of CD4 and GalCer on MEC membranes by use of a radiobinding assay (40). While expression of CCR5 and CXCR4 was not evaluated in the report by Toniolo et al, our findings are consistent with studies of murine mammary cells, which have been found to express CCR5 and CXCR4 (2). In addition, breast cancer studies have demonstrated the presence of CXCR4 in human mammary tissue by use of immunohistochemistry (31).…”

Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b–Mediated Malignant Progression

“…Ras drives cytokine secretion (36, 37, 51); thus, Let7 repression would feed forward to upregulate Ras and drive further IL6, IL8, and IP10 expression (19). IP10 upregulates CCL2 (51) and CCL2, in turn, stimulates CCL5 production by breast cancer cells (8); thus, coordinated upregulation of IP10, IL6, IL8, CCL2, and CCL5 following cancer cell invasion into fat would generate a self-perpetuating mechanism to support CSC expansion and metastasis even after cancer cell egress to other sites. Finally, coculture and cytokine exposures all upregulated c-Myc, potentially due to IL6-, IP10-, and CCL5-dependent suppression of miRs 34c-3p and/or 34-b, which target c-MYC, and also due to miR-302b-dependent c-MYC induction.…”

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

“…The expressions of EBV antigens in NPC tumor cells provide the targets for adoptive immunotherapy. [3][4][5][6] However, the poorly differentiated NPC is always characterized by the presence of a highly cellular lymphoid stroma admixed with tumor cells. 7 However, the role of local immunity surrounding NPC cells and the role EBV and viral products expressed in tumor cell remain unclear, which is associated with the expression of immune-related molecules including chemokines and receptors, HLA class I and II antigens, and co-stimulatory molecules and the role of EBV and viral products to alter the expression of immune-related molecules on tumor cells.…”