Abstract
Malignant pleural mesothelioma is a relatively rare, but devastating tumor, because of the difficulties in providing early diagnosis and effective treatments with conventional chemo- and radiotherapies. Patients usually present pleural effusions that can be used for diagnostic purposes by cytological analysis. This effusion cytology may take weeks or months to establish and has a limited sensitivity (30%–60%). Then, it is becoming increasingly urgent to develop alternative investigative methods to support the diagnosis of mesothelioma at an early stage when this cancer can be treated successfully. To this purpose, mechanobiology provides novel perspectives into the study of tumor onset and progression and new diagnostic tools for the mechanical characterization of tumor tissues. Here, we report a mechanical and biophysical characterization of malignant pleural mesothelioma cells as additional support to the diagnosis of pleural effusions. In particular, we examined a normal mesothelial cell line (Met5A) and two epithelioid mesothelioma cell lines (REN and MPP89), investigating how malignant transformation can influence cellular function like proliferation, cell migration, and cell spreading area with respect to the normal ones. These alterations also correlated with variations in cytoskeletal mechanical properties that, in turn, were measured on substrates mimicking the stiffness of patho-physiological ECM.
Highlights
An increasing number of studies report on how the recognition of interplays between microenvironment and cell mechanics could reveal pathophysiological disfunctions at different hierarchical tissue levels
The proliferation of normal mesothelial cells and Malignant pleural mesothelioma (MPM) cell lines was analyzed at 24 and 48 h from cell seeding. Both MPP89 and REN malignant cell lines exhibited higher proliferation compared to the benign one, but only a slight difference in the proliferation capability was observed between MPP89 and REN cells (Figure 1)
It has a long latency period and, it is often diagnosed in the late stages, when its resistance to conventional chemo- and radiotherapy is very strong
Summary
An increasing number of studies report on how the recognition of interplays between microenvironment and cell mechanics could reveal pathophysiological disfunctions at different hierarchical tissue levels. Through the formation of the adhesion structures at the cell–ECM interface, cells pulling and pushing on their surroundings remodel their microenvironment thanks to actomyosin- and cytoskeletalgenerated forces that, in turn, adapt themselves to biophysical cues and the mechanical state of ECM (Panzetta et al, 2017b). Such mechanism is deeply regulatory for cell behavior and, loss of the correct mechanical crosstalk between cells and extracellular environment could promote pathological imbalances. It is essential to consider in which way changes in biophysical signals and mechanical properties of matrix could influence the cancer journey from genesis to invasion
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