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Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane
Authors:Rosanna La Rocca  Rossana Tallerico  Almosawy Talib Hassan  Gobind Das  Lakshmikanth Tadepally  Marco Matteucci  Carlo Liberale  Maria Mesuraca  Domenica Scumaci  Francesco Gentile  Gheorghe Cojoc  Gerardo Perozziello  Antonio Ammendolia  Adriana Gallo  Klas K?rre  Giovanni Cuda  Patrizio Candeloro  Enzo Di Fabrizio  Ennio Carbone
Abstract:In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. 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. 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. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm−1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK) cells cytotoxic recognition.
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