Metastatic dormancy: a complex network between cancer stem cells and their microenvironment.
2014
Metastasis represents the major threat of
cancer progression and generally emerges years after the
detection of the primary tumor. An important ratelimiting 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.
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