Abstract 422: The role of CCL2 in the breast cancer tumor microenvironment and metastasis
| Autor: | Nicole Lavender, Ann Richmond, Jinming Yang, Jiqing Sai, Sergey V. Novitskiy |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Research. 75:422-422 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2015-422 |
| Popis: | Background: Although many effective breast cancer treatments exist, metastasis remains a major problem. Increasing evidence suggests that leukocyte-associated chemokines may play an important role in tumor growth and metastasis. For instance, recent data shows that reduction of CCL2 diminishes the recruitment of inflammatory monocytes to the tumor microenvironment (TME) and inhibits metastatic seeding to lung and bone marrow. Therefore, our goal is to examine the impact of CCL2 on the TME and pre-metastatic niche (i.e., lung). Methods: We are investigating how delivery of this chemokine affects breast tumor growth and metastasis by treating mice possessing highly metastatic and poorly metastatic tumors with CCL2, a CCL2 receptor (CCR2) antagonist, or vehicle for two weeks. Treatment will start 7 days after tumor implantation. On days 7, 14 or 21, tumors, lungs, and regional lymph nodes will be harvested and tumor size, number of metastases, and leukocyte infiltrate in both the tumor and the metastatic niche will be analyzed by FACS. This will allow us to fully characterize how intranasal delivery of CCL2 will affect the presence of mesenchymal stem cells (CD44+, CD73+, CD90+, CD146+/NOTCH3+, CD19-, CD45-), subsets of T cells, and myeloid cells in the TME or pre-metastatic niches. We will evaluate the intracellular cytokine and enzymatic profile (IL-4, IL-13, IL-17, ARG1 or IFNγ, IL-12, iNOS2) of Brefeldin-treated leukocytes to reveal whether they are pro- or anti-tumorigenic, respectively. Results: Our preliminary studies demonstrate that CCL2 enhances the release of hydrogen peroxide from neutrophils, a mechanism utilized by these cells to kill tumors cells. Furthermore, the addition of CCL2 to co-cultures of neutrophils and tumor cells increases the ability of neutrophils to kill tumor cells. Conclusions & Future Directions: Our data shows that delivery of CCL2 in vitro enhances the activity of neutrophils and their ability to kill tumor cells. Ongoing studies are examining the effects of in vivo and ex-vivo delivery of CCL2 or a CCR2 antagonist on primary tumor growth and metastasis. We will also investigate how administration of CCL2 or a receptor antagonist will affect the presence or absence of leukocytes in the TME. These findings will determine whether the addition of CCL2 during treatment of the primary tumor will provide a mechanism for reducing the potential of future breast cancer metastases. Citation Format: Nicole Lavender, Jiqing Sai, Jinming Yang, Sergey V. Novitskiy, Ann Richmond. The role of CCL2 in the breast cancer tumor microenvironment and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 422. doi:10.1158/1538-7445.AM2015-422 |
| Databáze: | OpenAIRE |
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