Description:
<jats:title>Abstract</jats:title>
<jats:p>Breast cancer is most frequently diagnosed cancer among women worldwide. Though advance in diagnosis and treatment strategies have prolonged disease-free survival (DFS) and overall survival (OS) for different molecular types of breast cancer patients, many patients initially benefit from chemotherapy but experience recurrence, metastasis, and ultimately death. Breast cancer stem cells (BCSCs) are tumor initiating cells with self-renewal, low differentiation, and high tumorigenicity and metastasis abilities. The ineffectiveness of conventional chemotherapy to eradicate BCSCs frequently results in therapy failure. Therefore, understanding the molecular pathways sustaining BCSC characteristics and targeting BCSCs will ultimately improve breast cancer treatments. Here, we found that activation of β-Catenin directly regulated CCL2 expression at the transcriptional level, and in turn, promoted tumor-associated macrophage (TAM) infiltration and M2 polarization. Moreover, crosstalk between the TAM and breast cancer cells increased secretion of CCL2, which promoted cancer progression by regulating BCSCs characteristics through feedback activation of β-Catenin. The combined inhibition of CCR2 and β-catenin synergistically suppressed breast cancer growth. The results described herein provide novel insights into our understanding how the β-Catenin-CCL2 feedback loop mediates the crosstalk between cancer stem cells and tumor-associated macrophages. They may also facilitate the development of useful therapeutic targets against BCSCs for breast cancer therapy.</jats:p>
<jats:p>Citation Format: Hao Liu, Bolin Liu. B-catenin-ccl2 axis regulates breast cancer stem cells via crosstalk between cancer cells and tumor-associated macrophages [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-16.</jats:p>