Abstract
Most cancer deaths are due to metastasis, and almost all cancers have their preferential metastatic organs, known as “organotropism metastasis”. Epithelial-mesenchymal plasticity has been described as heterogeneous and dynamic cellular differentiation states, supported by emerging experimental evidence from both molecular and morphological levels. Many molecular factors regulating epithelial-mesenchymal plasticity have tissue-specific and non-redundant properties. Reciprocally, cellular epithelial-mesenchymal plasticity contributes to shaping organ-specific pre-metastatic niche (PMN) including distinct local immune landscapes, mainly through secreted bioactive molecular factors. Here, we summarize recent progress on the involvement of tumor epithelial-mesenchymal plasticity in driving organotropic metastasis and regulating the function of different immune cells in organ-specific metastasis.
Highlights
The mechanisms of organotropism metastasis is one of the most unanswered questions in the field of cancer research
Tumor cells under partial Epithelial-mesenchymal transition (EMT) or hybrid EMT state, which means they keep both E and M properties, are likely to express or secret distinct bioactive factors and induce the formation of organ-specific pre-metastatic niche (PMN); at seeding organs, the partial MET cells are more adaptive to the organ microenvironment and to forming colonization; these partial EMT and MET cells are more resistant to immune attacks by altering the function of different immune cells in systemic circulation and local organs
We focus on the heterogeneous EMT and MET phenotypes in primary and metastatic tumors, the contribution of partial EMT and MET cells in organotropism metastasis, their regulation of the function of immune cells, and mostly, the secreted molecular factors regulating the cell–cell interactions in organ-specific tumor microenvironments
Summary
The mechanisms of organotropism metastasis is one of the most unanswered questions in the field of cancer research. Tumor cells undergoing EMT lose their cell–cell adhesion and apico-basal polarity and gain the ability to migrate individually and invade basement membrane and blood vessels. Upon intravasation, these cells stay in the bloodstream as circulating tumor cells (CTCs) and evade immune attacks until extravasation at distant organs to seed micro-metastases. These cells stay in the bloodstream as circulating tumor cells (CTCs) and evade immune attacks until extravasation at distant organs to seed micro-metastases During seeding, they undergo the reverse EMT process, MET, to regain their epithelial characteristics and form secondary tumors or macro-metastases [1]. We focus on the heterogeneous EMT and MET phenotypes in primary and metastatic tumors, the contribution of partial EMT and MET cells in organotropism metastasis, their regulation of the function of immune cells, and mostly, the secreted molecular factors regulating the cell–cell interactions in organ-specific tumor microenvironments
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