Accession Number : ADA594027


Title :   Priming the Tumor Immune Microenvironment Improves Immune Surveillance of Cancer Stem Cells and Prevents Cancer Recurrence


Descriptive Note : Final rept. 15 Sep 2010-14 Sep 2013


Corporate Author : SCRIPPS RESEARCH INST LA JOLLA CA


Personal Author(s) : Reisfeld, Ralph A ; Luo, Yunping


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a594027.pdf


Report Date : Oct 2013


Pagination or Media Count : 42


Abstract : Here, we report that Tumor-associated macrophages (TAMs) promote Cancer stem cell (CSC) -like phenotypes in murine breast cancer cells by up regulating their expression of Sox-2, resistance to chemotherapy, and increased tumorigenicity. Down regulation of Sox-2 in tumors blocked the ability of TAMs to induce these CSC-like phenotypes and inhibited tumor growth. We identified a novel EGFR/ Stat3/Sox-2 paracrine signaling pathway between macrophages and breast cancer cells and showed that this crosstalk was effectively blocked by small molecule inhibitors AG1478 or CDDO-Im against EGFR and Stat3, respectively. Therefore, our study identifies a novel role for TAMs in breast CSC regulation and establishes a rationale for targeting the EGFR/Stat3/Sox-2 signaling pathway for CSC therapy. Intratumoral injection of miR-19a-3p impaired the capacity of breast tumor cells to migrate and invade, suggesting it to play a critical role in induction of macrophage polarization and to be a useful therapeutic target for remodeling the tumor immune environment and thereby improve treatment of breast cancer.


Descriptors :   *BREAST CANCER , *NEOPLASMS , *STEM CELLS , CELLS(BIOLOGY) , CONTROL , IMMUNITY , INDUCTION SYSTEMS , INHIBITORS , MACROPHAGES , MAMMARY GLANDS , MEDICAL RESEARCH , MOLECULES , POLARIZATION , PRIMERS , REPORTS , RESISTANCE , SIGNALS , SKILLS , SURVEILLANCE , TARGETS , THERAPY


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE