About this Research Topic
Metastasis is the most serious challenge for cancer treatment. Metastasis still represents the major death-determinant and causes a significant reduction in the quality of life. A hallmark of the malignant process is the acquisition of an invasive phenotype that allows neoplastic cells to invade surrounding tissue and disseminate into specific organs. Early changes of the local microenvironment in distant organs are induced by primary tumor cells leading to the elaboration of a permissive niche for incoming circulating cancer cells. These modifications, characterized by the mobilization of non- malignant haematopoietic cells and the deposition of matrix components, precede the influx of metastatic cells.
The tumour microenvironment is a complex ecosystem consisting of cellular and non- cellular components. The cellular compartment includes not only tumour cells but also blood or lymphatic endothelial cells, pericytes, smooth muscle cells, (myo)fibroblasts, immune and inflammatory cells. In addition, it includes a small subpopulation of cancer stem cells (CSC), which are thought to be analogous to stem cells in normal tissue, dividing both to self-renew and to produce progeny that form the bulk of the tumour mass. CSC may be the source of metastatic cells as it is hypothesized that they can easily adopt the invasive genetic programme executed by stem and progenitor cells during normal organ development.
The non-cellular compartment consists of the various molecules of the extracellular matrix, whose composition directly and indirectly influences the phenotype of the cellular compartment. The process of cancer progression and metastatic dissemination is now viewed as a change of the homeostasis within the tumour microenvironment towards the accumulation of dissemination- promoting signals at the site of primary tumour formation, as well as in distant organ induced by both genetic and epigenetic stress.
Knowledge and control of the immediate microenvironment within the primary tumour, as well as in the distant organ susceptible to colonisation by metastatic cells derived from the primary tumour become as important as the conventional appreciation of knowledge and control of tumour cells themselves. We propose to present and discuss the data generated by the European FP7 MicroEnviMet consortium (n°201279). We welcome our colleagues to contribute to this Research Topic by reporting their findings and perspectives on the roles of the tumour microenvironment on metastatic dissemination, from in vitro models and mechanistic pathways to therapeutic strategies.
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