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Mechanical Properties of Cancer Cells
as a Biomarker for Stemness

Cancer stem cells (CSCs) are the driving force behind primary tumorigenesis and are assumed responsible for metastasis and cancer initiation at secondary sites. Defining the characteristics of CSCs has become an important subject in cancer research during the past decades. Although molecular surface expression levels have been used for CSC recognition, the clinical and prognostic impacts of these markers have remained a controversial issue. One of the potential biomarkers for CSCs is their mechanical properties, which refer to the physical characteristics of cells, such as stiffness, elasticity, viscosity, and deformability. Mechanical properties can affect the ability of cells to migrate, invade, adhere, and interact with other cells and the extracellular matrix. Moreover, mechanical properties can be influenced by the molecular and structural changes that occur in cells during cancer progression and therapy.Our results have established rheological properties as a potential biomarker for CSCs which can eventually help with the development of new cancer diagnostic and therapeutic methods.

Deformability of Cancer Stem Cells
in Correlation with Invasiveness

For cancer stem cells (CSCs) to complete the process of metastasis, not only they need to have the ability to initiate the journey (by separating from the primary tumor) and the capacity for self-renewal and proliferation (at the secondary tumor) but also, they should survive the physical interactions and mechanical forces which they encounter throughout the process. The cytoplasm of the cell is a complex structure, which (depending on the deformation rate) might behave like an elastic or viscous material. Our findings suggest that CSCs might act like an elastic material during extravasation and intravasation (high deformation rate), whereas they might behave like a viscous material under blood shear flow (low deformation rate). The deformability of CSCs equips them to balance an increase in shear by increasing the contact area or by decreasing the inclination angle of microvilli, leading to stable rolling velocities at various levels of shear stress. Our results indicate that adaptive rheology at different stages of metastasis is a critical factor for CSCs to complete the process successfully.

Mechanosensing in Tumor Microenvironment

Mechanosensing in the tumor microenvironment refers to the ability of cancer cells and surrounding cells to detect and respond to mechanical forces and changes in tissue stiffness within the tumor's surroundings. This phenomenon plays a critical role in cancer progression and behavior.Tumors are not isolated entities; they exist within a dynamic microenvironment composed of various cell types, extracellular matrix (ECM), and biochemical cues. Mechanical forces, such as tissue stiffness, compression, and fluid flow, are prevalent within this microenvironment and can profoundly impact tumor growth, invasion, and metastasis.Cancer cells and surrounding cells possess mechanosensors, which are specialized molecules and structures that can perceive mechanical cues. These mechanosensors include integrins, focal adhesions, and other signaling molecules. When mechanical forces are applied to these receptors, they activate intricate signaling pathways that influence cell behavior.Understanding the role of mechanosensing in the tumor microenvironment has important implications for cancer research and therapy development. Researchers are exploring ways to target mechanosensitive pathways to impede tumor growth, invasion, and metastasis. Additionally, therapies that alter the stiffness of the tumor microenvironment may enhance drug delivery and improve treatment outcomes. Overall, mechanosensing is a complex and emerging field that sheds light on the intricate interplay between mechanical forces and cancer biology.

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