Inhibition of Anti-Inflammatory Macrophage Phenotype Reduces Tumour Growth in Mouse Models of Brain Metastasis.

Breast cancer brain metastasis is a significant clinical problem and carries a poor prognosis. Although it is well-established that macrophages are a primary component of the brain metastasis microenvironment, the role of blood-derived macrophages (BDM) and brain-resident microglia in the progression of brain metastases remains uncertain. The aim of this study, therefore, was to determine the role, specifically, of pro- and anti-inflammatory BDM and microglial phenotypes on metastasis progression.

Automated Co-in Situ Hybridization and Immunofluorescence Using Archival Tumor Tissue.

In situ hybridization (ISH) and immunohistochemistry (IHC) are valuable tools for molecular pathology and cancer research. Recent advances in multiplex technology, assay automation, and digital image analysis have enabled the development of co-ISH IHC or immunofluorescence (IF) methods, which allow researchers to simultaneously view and quantify expression of mRNA and protein within the preserved tissue spatial context. These data are vital to the study of the control of gene expression in the complex tumor microenvironment.

Anti-inflammatory Microglia/Macrophages As a Potential Therapeutic Target in Brain Metastasis.

Brain metastasis is a common complication of cancer patients and is associated with poor survival. Histological data from patients with brain metastases suggest that microglia are the major immune population activated around the metastatic foci. Microglia and macrophages have the ability to polarize to different phenotypes and to exert both tumorigenic and cytotoxic effects.

Early Diagnosis of Brain Metastases Using a Biofluids-Metabolomics Approach in Mice.

Over 20% of cancer patients will develop brain metastases. Prognosis is currently extremely poor, largely owing to late-stage diagnosis. We hypothesized that biofluid metabolomics could detect tumours at the micrometastatic stage, prior to the current clinical gold-standard of blood-brain barrier breakdown.

Disruption of tumour-host communication by downregulation of LFA-1 reduces COX-2 and e-NOS expression and inhibits brain metastasis growth.

Over 20% of cancer patients will suffer metastatic spread to the brain, and prognosis remains poor. Communication between tumour cells and host tissue is essential during metastasis, yet little is known of the processes underlying such interactions in the brain.Here we test the hypothesis that cross-talk between tumour cells and host brain cells, through tumour cell leukocyte function associated protein-1 (LFA-1), is critical in metastasis development.

Regulation of CXCR4 gene expression in breast cancer cells under diverse stress conditions.

Chronic inflammation is a critical component in breast cancer progression. Pro-inflammatory mediators along with growth/survival factors within the tumor microenvironment potentiate the expression of pro-inflammatory cytokines (IL-1, IL-6, TNF-α), chemotactic cytokines and their receptors (CXCR4, CXCL12, CXCL8) and angiogenic factors (VEGF) that often overcome the effect of anti-inflammatory molecules (IL-4, IL-10) thus evading the host's antitumor immunity. Detailed knowledge, therefore, of the regulatory mechanisms determining cytokine levels is essential to understand the pathogenesis of breast cancer.