A novel model of dormancy for bone metastatic breast cancer cells

Research output: Contribution to journalArticle

Abstract

Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy.

Details

Authors
  • Rebecca Marlow
  • Gabriella Honeth
  • Sara Lombardi
  • Massimiliano Cariati
  • Sonya Hessey
  • Aikaterini Pipili
  • Veronica Mariotti
  • Bharath Buchupalli
  • Katie Foster
  • Dominique Bonnet
  • Agamemnon Grigoriadis
  • Pranela Rameshwar
  • Anand Purushotham
  • Andrew Tutt
  • Gabriela Dontu
Organisations
External organisations
  • King's College London
Research areas and keywords

Keywords

  • Animals, Bone Marrow Cells, Bone Neoplasms, Breast Neoplasms, Cell Cycle Checkpoints, Cells, Cultured, Female, Human Umbilical Vein Endothelial Cells, Humans, MCF-7 Cells, Mice, Mice, Inbred NOD, Mice, SCID, Models, Biological, Neoplastic Stem Cells, Stem Cell Niche, Stromal Cells, Tumor Microenvironment, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)6886-99
Number of pages14
JournalCancer Research
Volume73
Issue number23
Publication statusPublished - 2013 Dec 1
Publication categoryResearch
Peer-reviewedYes