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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, Y; Yang, P; Sun, T; Li, D; Xu, X; Rui, Y; Li, C; Chong, M; Ibrahim, T; Mercatali, L; Amadori, D; Lu, X; Xie, D; Li, Q-J; Wang, X-F

Published Date

  • March 2013

Published In

Volume / Issue

  • 15 / 3

Start / End Page

  • 284 - 294

PubMed ID

  • 23396050

Pubmed Central ID

  • PMC3672398

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

Digital Object Identifier (DOI)

  • 10.1038/ncb2690


  • eng

Conference Location

  • England