Accession Number : AD1011673


Title :   Alpha2-Adrenergic Receptors and Breast Tumor Stroma: A Novel Pathway Driving Breast Cancer Growth and Metastasis


Descriptive Note : Technical Report,30 Sep 2014,29 Sep 2015


Corporate Author : University of Rochester Rochester United States


Personal Author(s) : Madden,Kelley S


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1011673.pdf


Report Date : 01 Oct 2015


Pagination or Media Count : 16


Abstract : Breast cancer metastasis is driven by sympathetic nervous system (SNS) and -adrenergic receptor (-AR) activation, but the role for 2-AR, a major class of SNS receptors, has not been elucidated. The goal of this proposal is to characterize the effects of dexmedetomidine (DEX), a highly selective 2-AR agonist, on tumor metastasis in preclinical models of breast cancer. Using EO771, a metastatic mammary adenocarcinoma in C57BL/6/c mice, 2-AR activation increased tumor growth, but not metastasis to the lungs. In C57BL/6 mice treated with a 2-AR-selective agonist, EO771 tumor growth was inhibited with no corresponding change in lung metastasis. In both models of AR activation, tumor collagen was not altered as measured by multiphoton SHG imaging or by standard immunostaining. In BALB/c mice with 4T1 tumors, 2-AR elicited a tumor inhibitory environment that was not detected in C57BL/6 mice with EO771 tumors. In both mouse strains, unlike 2-AR activation, -AR activation alters myeloid populations, especially the immunosuppressive myeloid derived suppressor cells. A breast cancer cell line derived from the MMTV-PyMT mice was shown to possess functional alpha2-AR and -AR. We also show progress made in developing a model of micrometastasis after primary tumor dissection.


Descriptors :   breast cancer , metastasis , collagen , neoplasms , Fibroblasts , mice , models , myeloid cells , cell line , stromal cells


Distribution Statement : APPROVED FOR PUBLIC RELEASE