A novel model of dormancy for bone metastatic breast cancer cells

Rebecca Marlow, Gabriella Honeth, Sara Lombardi, Massimiliano Cariati, Sonya M Hessey, Aikaterini Pipili, Veronica Mariotti, Bharath Buchupalli, Katie Foster, Dominique Bonnet, Agamemnon Grigoriadis, Anand Purushotham, Andrew Tutt, Gabriela Dontu

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Mortality of breast cancer patients 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 co-cultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant, and 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.
Original languageEnglish
Pages (from-to)6886-6899
Number of pages14
JournalCancer Research
Volume73
Issue number23
DOIs
Publication statusPublished - Dec 2013

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