Prometastatic Molecular Profiles in Breast Tumors From Socially Isolated Women

JNCI Cancer Spectrum

Sullivan, Peggy¹  Ganz, Patricia A¹  Mercado, Fernando²  Arevalo, Jesusa³  Asher, Arash⁴  Shiao, Stephen L⁴  Bower, Julienne E⁵  Atienza, Robert⁶  Lamkin, Donald M⁷  Cole, Steve W⁷ 

[1] Cousins Center for Psychoneuroimmunology, UCLA, Los Angeles, CA;Department of Biomedical Sciences;Department of Pathology and Laboratory Medicine;Department of Psychiatry and Biobehavioral Sciences;Department of Psychology;Department of Radiation Oncology;Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA

关键词: breast neoplasms;    social isolation;    neoplasms;    gene expression;    breast cancer;    lymphatic vessels;    genes;    macrophages;    signal transduction;   

DOI  :  10.1093/jncics/pky029

学科分类：肿瘤学

来源: Oxford University Press

【 摘 要 】

BackgroundSocial isolation is associated with accelerated breast cancer progression and increased disease recurrence and mortality, but the underlying biological mechanisms remain poorly understood. In preclinical models, beta-adrenergic signaling from fight-or-flight stress responses can stimulate prometastatic processes in the tumor microenvironment including upregulation of M2 macrophages, epithelial–mesenchymal transition (EMT), and lymphovascular invasion. This study examines whether the same pathways are upregulated in breast tumors from socially isolated cancer patients.MethodsEMT and M1/M2 macrophage gene expression programs were analyzed by genome-wide transcriptional profiling, and lymphatic and vascular density were assessed by immunohistochemistry in primary tumors from 56 early-stage breast cancer patients who were part of the UCLA RISE study. Social isolation was quantified by the Social Provisions Scale, and disease characteristics were assessed by medical record review. General linear models were used to quantify differential gene expression across risk factor groups. Linear regression models were used to examine associations between social isolation and lymphovascular invasion.ResultsTumors from socially isolated patients showed upregulated expression of genes involved in EMT (average score difference = +0.080 log2 mRNA abundance ± 0.034 standard error) and M2 macrophage polarization (+0.033 ± 0.014) as well as increased density of lymphatic vessels (β= –.29) but no difference in blood vessel density. TELiS promoter–based bioinformatics analyses indicated activation of CREB family transcription factors that mediate the gene-regulatory effects of β-adrenergic signaling (log2 fold-difference in promoter binding site prevalence: mean ± standard error = +0.49 ± 0.19). ConclusionsPrimary breast tumors from socially isolated patients show multiple prometastatic molecular alterations, providing a plausible biological pathway through which poor social support may accelerate breast cancer progression and defining new targets for intervention.

【 授权许可】

CC BY-NC-ND