Circulating CCL2 and CXCL8 chemokine levels and receptor interactions differ in African-Americans and Caucasians with breast cancer

Document Type

Conference Proceeding

Publication Date

8-1-2018

Publication Title

Mol Cancer Res

Abstract

In 2013, the breast cancer mortality rate of African-American (AA) women in the U.S. was significantly higher than Caucasian women, even though incidence rates were about equal. Undoubtedly, access to health care and socioeconomic status could contribute to this health disparities gap, but inherent biologic differences may also be a contributing factor. The purpose of this study is to determine if differences in immunobiology, particularly the abundance of two proinflammatory chemokines, differs between AA and Caucasian women with breast cancer. Differences in these signaling molecules can affect the migration of immune cells, in addition to having a significant effect on cancer progression and tumor biology. We are also interested in the interactions between these chemokines and one of their receptors, ACKR1, which harbors ancestry-specific alleles. Generally, those of AA descent express less of this receptor on their tumor cells, producing a yet to be determined immune response when it comes to breast cancer. Using plasma samples obtained from breast cancer patients pretreatment, in addition to plasma samples from control patients, we were able to determine any differences in chemokine protein levels from these participants using a Luminex immunoassay. Our molecules of interest, CCL2 (MCP-1) and CXCL8 (IL-8), were both chosen due to their ability to influence immune cell migration, in addition to angiogenesis and cancer cell progression. From our analysis, race-specific differences were observed for these particular chemokines between AA and Caucasians with breast cancer. When considering CCL2, it appears that AA had significantly less CCL2 present in circulation when compared to Caucasians. For CXCL8, the median concentration for AA cancer patients was much lower than that of the Caucasian group. The presence or absence of ACKR1 on the tumors of these patients also seems to play a role in circulating chemokine levels, with higher circulating levels being associated with those who have the receptor present on tumor cells. Overall, there appear to be biologic differences in immune response between AA and Caucasians with breast cancer, especially when considering CCL2 and CXCL8, and their interactions with ACKR1. This difference could account for variations in treatment responses, in addition to differences in breast cancer aggressiveness and progression seen within these two groups.

Volume

16

Issue

8

First Page

27

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