Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigens, CD24
  • Antigens, CD44
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Cell Line, Tumor
  • Cell Survival
  • Cells, Cultured
  • Coculture Techniques
  • Homeodomain Proteins
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • MCF-7 Cells
  • Membrane Proteins
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Microscopy, Confocal
  • Neoplasm Metastasis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serrate-Jagged Proteins
  • Transcription Factor HES-1
  • Transplantation, Heterologous

MeSH Major

  • Breast Neoplasms
  • Cellular Microenvironment
  • Endothelial Cells
  • Neoplastic Stem Cells
  • Receptors, Notch

abstract

  • Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.

publication date

  • 2014

has subject area

  • Animals
  • Antigens, CD24
  • Antigens, CD44
  • Basic Helix-Loop-Helix Transcription Factors
  • Breast Neoplasms
  • Calcium-Binding Proteins
  • Cell Line, Tumor
  • Cell Survival
  • Cells, Cultured
  • Cellular Microenvironment
  • Coculture Techniques
  • Endothelial Cells
  • Homeodomain Proteins
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • MCF-7 Cells
  • Membrane Proteins
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Microscopy, Confocal
  • Neoplasm Metastasis
  • Neoplastic Stem Cells
  • Receptors, Notch
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serrate-Jagged Proteins
  • Transcription Factor HES-1
  • Transplantation, Heterologous

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4224483

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0112424

PubMed ID

  • 25380486

Additional Document Info

start page

  • e112424

volume

  • 9

number

  • 11