Mechanical stress downregulates MHC class I expression on human cancer cell membrane.

Rosanna La Rocca,Carlo Liberale,Marco Matteucci,Lakshmikanth Tadepally,Almosawy Talib Hassan,Ennio Carbone,Adriana Gallo,Antonio Ammendolia,Gheorghe Cojoc,Francesco Gentile,Gerardo Perozziello,Giovanni Cuda,Patrizio Candeloro,Gobind Das,Maria Mesuraca,Klas Kärre,Domenica Scumaci,Rossana Tallerico,E Di Fabrizio

doi:10.1371/journal.pone.0111758

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.

Highlights

In nature, cells are continually exposed to physical, chemical and biological stresses
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 [6]
To understand the potential effects of mechanical stress on cell immunogenicity, cancer and healthy cells were mechanically stressed with a micropump device and shock waves

Summary

Introduction

Cells are continually exposed to physical, chemical and biological stresses. Physical stress is involved in the pathophysiology of several human diseases, such as inflammation and cancer In both conditions, an alteration in the chemical-physical extracellular matrix (ECM) environment is associated with the pathogenesis of these diseases. The optical stretcher is based on a double-beam optical trap [3, 4] in which two opponent and identical laser beams trap a cell in the middle. 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 [5]. Inflammatory breast cancer is known to exert a mechanical load due to the ECM changes, potentially leading to a higher metastatic potential [9]

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