Microenvironments Dictating Tumor Cell Dormancy
- 21 April 2012
- book chapter
- review article
- Published by Springer Science and Business Media LLC in Recent Results in Cancer Research
- Vol. 195, 25-39
- https://doi.org/10.1007/978-3-642-28160-0_3
Abstract
The mechanisms driving dormancy of disseminated tumor cells (DTCs) remain largely unknown. Here, we discuss experimental evidence and theoretical frameworks that support three potential scenarios contributing to tumor cell dormancy. The first scenario proposes that DTCs from invasive cancers activate stress signals in response to the dissemination process and/or a growth suppressive target organ microenvironment inducing dormancy. The second scenario asks whether therapy and/or micro-environmental stress conditions (e.g. hypoxia) acting on primary tumor cells carrying specific gene signatures prime new DTCs to enter dormancy in a matching target organ microenvironment that can also control the timing of DTC dormancy. The third and final scenario proposes that early dissemination contributes a population of DTCs that are unfit for immediate expansion and survive mostly in an arrested state well after primary tumor surgery, until genetic and/or epigenetic mechanisms activate their proliferation. We propose that DTC dormancy is ultimately a survival strategy that when targeted will eradicate dormant DTCs preventing metastasis. For these non-mutually exclusive scenarios we review experimental and clinical evidence in their support.Keywords
This publication has 65 references indexed in Scilit:
- Tumor Self-Seeding by Circulating Cancer CellsCell, 2009
- Microenvironmental regulation of metastasisNature Reviews Cancer, 2008
- GATA-3 Links Tumor Differentiation and Dissemination in a Luminal Breast Cancer ModelCancer Cell, 2008
- Systemic Spread Is an Early Step in Breast CancerCancer Cell, 2008
- Models, mechanisms and clinical evidence for cancer dormancyNature Reviews Cancer, 2007
- Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancerCancer Cell, 2005
- A Pooled Analysis of Bone Marrow Micrometastasis in Breast CancerNew England Journal of Medicine, 2005
- Dissecting the metastatic cascadeNature Reviews Cancer, 2004
- Tumor doubling times in metastatic malignant melanoma of the uvea Tumor progression before and after treatmentOphthalmology, 2000
- Cytokeratin-Positive Cells in the Bone Marrow and Survival of Patients with Stage I, II, or III Breast CancerNew England Journal of Medicine, 2000