title: Metastatic dormancy: a complex network between cancer stem cells and their microenvironment.
abstract: Metastasis represents the major threat of cancer progression and generally emerges years after the detection of the primary tumor. An important rate-limiting step resides in cellular dormancy, where a disseminated tumor cell remains in a quiescent state at a remote organ. Herein we review the molecular mechanisms leading to tumor dormancy, mainly in regards to cellular quiescence and the tumor microenvironment. Based on the current published literature, we provide evidence that links the cancer stem cell (CSC) theory with dormancy and metastasis. Once a disseminated tumor cell reaches a target tissue, a tight regulation imposed by the foreign microenvironment will dictate the fate of these cells, which implies a balance in the secretion of soluble factors, modulation of the extracellular matrix and the angiogenic switch. We investigate thoroughly whether the CSC theory could also apply to metastasis initiation. In fact, the resistance of CSCs to therapy, leading to the minimal residual disease and cellular quiescence phenotypes, predisposes for the development of metastases. Finally, we describe the new technologies available for the identification of circulating tumor cells (CTCs), as well as their clinical relevance in dormancy of metastatic cancer patients.
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bleau
authors.affiliation: Section of Magnetic Resonance, Cancer Research UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Surrey, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Agliano
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Larzabal
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), and Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain.
authors.forename: Arrate Lopez
authors.initials: AL
authors.lastname: de Aberasturi
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), and Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain. acalvo@unav.es.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calvo
mesh_terms: D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D059016:Tumor Microenvironment / Q000502:physiology*