Finally, inflammatory breast cancer is known to exert a mechanical load due to the ECM changes, potentially leading to a higher metastatic potential. It has been also demonstrated that the increment of exogenous forces lead to an increased cell proliferation rate and induce tumor-like phenotypic changes. It has been shown that ECM-mediated isometric forces are sensed by integrins, which regulate the phosphorylation of mechano-transducer kinases, such as ERK and Rho. A relationship between ECM stiffness and tumor transformation has been described. Furthermore, elasticity and contractility of different tumor cells may change with the progression of the disease, with an increased elasticity of the cancerous compared with the healthy cells. This method can be used to measure the elastic and contractile properties of many cells, as it is known that the cell's ability to contract is very important for migration and proliferation. Unlike other tools, the optical stretcher is based on a double-beam optical trap, in which two opponent and identical laser beams trap a cell in the middle. Furthermore, to determine how much a cell can be deformed, a device called “optical stretcher” was developed. In recent years, novel tools, such as atomic force microscopy, have been developed to analyse changes in cells elasticity related to physical changes in the extracellular matrix compartment. Moreover, physical forces play a significant role in metastatic progression. In both conditions, an alteration in the chemical-physical extracellular matrix (ECM) environment is associated with the pathogenesis of these diseases. Physical stress is involved in the pathophysiology of several human diseases, such as inflammation and cancer. In the past, physical changes occurring in pathological tissues were taken into account by the physicians as valuable diagnostic indicators. In nature, cells are continually exposed to physical, chemical and biological stresses. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. Giovanni Cuda has been supported by PON01_02834 Prometeo (Ministry of Education and Research) and PONa3_00435 (Ministry of Education and Research). Rossana Tallerico is a Post Doc awarded by triennial fellowships “Luciana Selce” FIRC. All relevant data are within the paper and its Supporting Information files.įunding: Ennio Carbone's work has been supported by a UICC International Cancer Technology Transfer Fellowship, grant AIRC-IG 10189, and grant AIRC 15521. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: The authors confirm that all data underlying the findings are fully available without restriction. Received: ApAccepted: SeptemPublished: December 26, 2014Ĭopyright: © 2014 La Rocca et al. PLoS ONE 9(12):Įditor: Laurent Kreplak, Dalhousie University, Canada (2014) Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK) cells cytotoxic recognition.Ĭitation: La Rocca R, Tallerico R, Talib Hassan A, Das G, Tadepally L, Matteucci M, et al. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm −1, indicated a relative concentration variation of MHC class I. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells) was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal), depending on the devices used. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. In this work, we employed two different strategies to mechanically stress cancer cells. In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death.
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