ECM Mechanoregulation in Malignant Pleural Mesothelioma

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.

Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure

“…Therefore, with the exception of the presence of fibers, neoplastic cells are not distinguished from healthy cells by cellular morphology. In accordance with Panzetta et al 51 morphology alone is not sufficient to discriminate malignant cells from benign cells. In addition, the in vitro viability of MeT-5A and JU77 from 6 to 72 h exposure to FE has been evaluated to examine the effects of FE fibers upon mesothelium and MM.…”

Role of the mechanical microenvironment on CD-44 expression of breast adenocarcinoma in response to radiotherapy

“…Noteworthy is the fact that alterations in the structure of the CSK exert a significant impact on the motility and heightened metastatic propensity of cancer cells. Additionally, changes in the composition and stiffness of the surrounding tissue (i.e., ECM) can induce cells’ growth and activate processes that lead to spreading and invasion 11 – 14 . In the current context, the research landscape has extensively explored the RT impact on cell behavior, neglecting that produced on ECM content and structural organization 11 , 15 – 18 .…”

3D spheroid-microvasculature-on-a-chip for tumor-endothelium mechanobiology interplay

“…3D multicellular tumor spheroid is a promising model that mimics the in vivo solid tumor. The tumor spheroids have potential to bridge the gap between a 2D monolayer cell culture and in vivo studies by providing similar in vivo biomechanical integrities, such as spatial interactions of cells with surrounding cells and extracellular matrix [35][36][37] in the tumor microenvironment [38]. In this regard, we employed a liquid dome model to produce more than 200 tumor spheroids in less than a day as previously reported [39].…”