Journal Article

miR-126 and miR-126 repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis

Xie, Dong, Wang, Xiao-Fan, Lu, Xincheng, Amadori, Dino, Sun, Tao, Li, Chaoran, Xu, Xin, Chong, Mengyang, Li, Qi-Jing, Zhang, Yun, Mercatali, Laura, Li, Dong, Ibrahim, Toni, Rui, Yaocheng, Yang, Pengyuan

2013

Overview

The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126 * , a microRNA pair derived from a single precursor, independently suppress the sequential recruitment of mesenchymal stem cells and inflammatory monocytes into the tumour stroma to inhibit lung metastasis by breast tumour cells in a mouse xenograft model. miR-126/miR-126 * directly inhibit stromal cell-derived factor-1 alpha (SDF-1α) expression, and indirectly suppress the expression of chemokine (C–C motif) ligand 2 (Ccl2) by cancer cells in an SDF-1α-dependent manner. miR-126/miR-126 * expression is downregulated in cancer cells by promoter methylation of their host gene Egfl7 . These findings determine how this microRNA pair alters the composition of the primary tumour microenvironment to favour breast cancer metastasis, and demonstrate a correlation between miR-126/126 * downregulation and poor metastasis-free survival of breast cancer patients. Wang and colleagues show that miR-126 and miR-126 * suppress metastasis by inhibiting the production of the Sdf-1α cytokine in mouse mammary tumours, resulting in decreased recruitment of mesenchymal stem cells and inflammatory monocytes to the tumour stroma.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/384/331 / 631/67/1347 / 631/67/322 / 631/80/86 / Analysis / Angiogenesis / Animals / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Blotting, Western / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Breast Neoplasms - prevention & control / Cancer Research / Cell Adhesion / Cell Biology / Cell Differentiation / Cell Movement / Cell Proliferation / Cells, Cultured / Chemokine CXCL12 - genetics / Chemokine CXCL12 - metabolism / Development and progression / Developmental Biology / DNA Methylation / Female / Gene Expression Profiling / Genetic aspects / Humans / Immunoenzyme Techniques / Immunoprecipitation / Inflammation - metabolism / Inflammation - pathology / Invasiveness / Life Sciences / Lung Neoplasms - genetics / Lung Neoplasms - prevention & control / Lung Neoplasms - secondary / Mesenchymal Stromal Cells - metabolism / Mesenchymal Stromal Cells - pathology / Metastasis / Methylation / Mice / Mice, Inbred BALB C / MicroRNA / MicroRNAs / MicroRNAs - genetics / Monocytes - metabolism / Monocytes - pathology / Oligonucleotide Array Sequence Analysis / Oncology / Physiological aspects / Promoter Regions, Genetic - genetics / Proteins - genetics / Proteins - metabolism / Real-Time Polymerase Chain Reaction / Reverse Transcriptase Polymerase Chain Reaction / Risk factors / RNA, Messenger - genetics / Stem Cells / Stromal Cells - metabolism / Stromal Cells - pathology / Tumor Microenvironment / Tumors