Mechanobiology and survival strategies of circulating tumor cells: a process towards the invasive and metastatic phenotype

Abstract

Metastatic progression is the deadliest feature of cancer. Cancer cell growth, invasion, intravasation, circulation, arrest/adhesion and extravasation require specific mechanical properties to allow cell survival and the completion of the metastatic cascade. Circulating tumor cells (CTCs) come into contact with the capillary bed during extravasation/intravasation at the beginning of the metastatic cascade. However, CTC mechanobiology and survival strategies in the bloodstream, and specifically in the microcirculation, are not well known. A fraction of CTCs can extravasate and colonize distant areas despite the biomechanical constriction forces that are exerted by the microcirculation and that strongly decrease tumor cell survival. Furthermore, accumulating evidence shows that several CTC adaptations, via molecular factors and interactions with blood components (e.g., immune cells and platelets inside capillaries), may promote metastasis formation. To better understand CTC journey in the microcirculation as part of the metastatic cascade, we reviewed how CTC mechanobiology and interaction with other cell types in the bloodstream help them to survive the harsh conditions in the circulatory system and to metastasize in distant organs.

Liquid Biopsy

“…These CTM exhibit distinct phenotypic and molecular characteristics compared to single CTCs and demonstrate higher metastatic potential and resistance to apoptosis compared to their single-cell counterparts [55]. The microemboli are composed of different cell types, including immune cells such as neutrophils or platelets [56]. CTM exhibits a different molecular profile compared to single cells.…”

Multiplex, high-throughput method to study cancer and immune cell mechanotransduction

“…Physiological FSS in humans ranges from 0.5 to 30.0 dyn cm −2 (0.05–3 Pa) in veins and arteries, in which shear rates typically range from 160 s −1 to 900 s −1 12 , 13 . FSS can reach 100 dyn cm −2 (10 Pa) at valve leaflets within the heart 7 , 14 , 15 and can exceed these intensities in cancer patients who present stenosis 16 – 18 . FSS can also reach peak values over 1000 dyn cm −2 (100 Pa) at vessel bifurcations or turbulent flows near the heart 19 – 24 .…”

First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof‐of‐concept study

“…Indeed, once released from the immunosuppressive tumor microenvironment, many tumor cells are likely to be attacked by immune cells. Moreover, CTCs face shear stress that strongly affects their survival 6 . However, CTCs can escape the immune system by undergoing significant changes, such as epithelial‐to‐mesenchymal transition (EMT), 7 or by being protected by platelets 8 .…”

“…Moreover, CTCs face shear stress that strongly affects their survival. 6 However, CTCs can escape the immune system by undergoing significant changes, such as epithelial‐to‐mesenchymal transition (EMT), 7 or by being protected by platelets. 8 Moreover, the CTC microenvironment supports their immune surveillance evasion and promotes their dissemination.…”