Date of Award

8-1-2019

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Ran, Sophia

Abstract

Inflammatory cytokines and chemokines are known to promote tumor cell survival, invasion, the formation of blood and lymphatic vessels, and hence, metastasis. We previously showed that a pro-inflammatory pathway regulated by Toll-like Receptor-4 (TLR4) can be activated in human breast cancer (BC) cell lines by a clinical chemotherapeutic drug, paclitaxel (PXL). Prior data showed that PXL treatment of TLR4+ tumors in vivo increased inflammation and tumor spread. Here, we used two BC models based on MDA-MB-231 and HCC1806 cell lines. Transcript expression of 123 cytokines in vitro and in vivo was determined by qRT-PCR. We found that 18 and 26 cytokines were upregulated by nanoparticle albumin-bound paclitaxel (nab-PXL) in 231TLR4+ cells and in 1806TLR4+ cells, respectively. Upregulation of cytokines was observed in cultured cells and in tumor models in vivo. Furthermore, fourteen cytokines (11.3% of total) were induced by nab-PXL in both tumor models suggesting that these targets are upregulated by PXL regardless of genetic makeup of tumor cells. We also confirmed the expression of these cytokines on protein level by ELISA. We found that expression of CCL20 and CXCL1 proteins is consistent with transcript expression detected by qRT-PCR. Taken together, CCL20 and CXCL1 can be the potential targets for further study, and they may have the capacity to recruit myeloid-derived lymphatic endothelial cell progenitors to the tumor site to promote lymphangiogenesis in breast cancer.

Available for download on Tuesday, April 14, 2020

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