Abstract
Metastatic progression, which begins with the invasion and migration of tumor cells from a primary tumor, marks a major turning point in the evolution of cancer. Indeed, it eventually leads to the formation of secondary tumors, the metastases, which are very often responsible for the patient's death. Understanding the mechanisms controlling the different steps of this process, as well as those explaining the fundamental phenomenon of organotropism (i.e. the distribution of metastases in distant organs by a non-random and tumor-specific process), is essential to define new innovative therapeutic solutions. In this review paper, we will present how biomechanics is an essential element to this understanding, and will emphasize the importance of this orthogonal and promising angle of study as well as our laboratory's focus on the late stages of dissemination, arrest and extravasation of circulating cancer cells and factors secreted by the primary tumor such as extracellular vesicles.
Highlights
Metastatic progression—the last step of the multistage carcinogenesis process—is leading to the development of metastases that are usually responsible for the death of cancer patients [1, 2]
Extracellular vesicles (EVs) in particular—small lipid bilayer particles that serve as signaling cargoes and which can be quickly cleared from the blood by intravascular macrophages/monocytes [18] and endothelial cells of the pre-metastatic niche (PMN)—have been demonstrated to exhibit specific organotropism depending on their primary tumor of origin, a feature made possible by the exposure of a variable repertoire of surface adhesion molecules [19]
We recently demonstrated that fluid forces are key in activating flow sensing receptors and promote extravasation processes and metastasis
Summary
Metastatic progression—the last step of the multistage carcinogenesis process—is leading to the development of metastases that are usually responsible for the death of cancer patients [1, 2]. Extracellular vesicles (EVs) in particular—small lipid bilayer particles that serve as signaling cargoes and which can be quickly cleared from the blood by intravascular macrophages/monocytes [18] and endothelial cells of the PMNs—have been demonstrated to exhibit specific organotropism depending on their primary tumor of origin, a feature made possible by the exposure of a variable repertoire of surface adhesion molecules [19] Because they are transported by the blood flow, these non-inert circulating objects may “stop” in specific vascular regions as a function of their adhesive potential and the hemodynamic forces at play [18]. The newformed metastases will, in turn, potentially initiate their own process of tumor progression and metastasis in the manner of the primary tumor, and dramatically accelerate the worsening of the cancer patient’s health condition
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