Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy.

Mengdan Chen,Shusen Xie,Zhenghong Zhang,Zhengchao Wang,Weiwei Ruan,Yuhua Wang,Hongqin Yang,Jinshu Zeng

doi:10.3762/bjnano.11.45

Abstract

The mechanical properties of cells could serve as an indicator for disease progression and early cancer diagnosis. This study utilized atomic force microscopy (AFM) to measure the viscoelastic properties of ovarian cancer cells and then examined the association with the invasion of ovarian cancer at the level of living single cells. Elasticity and viscosity of the ovarian cancer cells OVCAR-3 and HO-8910 are significantly lower than those of the human ovarian surface epithelial cell (HOSEpiC) control. Further examination found a dramatic increase of migration/invasion and an obvious decease of microfilament density in OVCAR-3 and HO-8910 cells. Also, there was a significant relationship between viscoelastic and biological properties among these cells. In addition, the elasticity was significantly increased in OVCAR-3 and HO-8910 cells after the treatment with the anticancer compound echinomycin (Ech), while no obvious change was found in HOSEpiC cells after Ech treatment. Interestingly, Ech seemed to have no effect on the viscosity of the cells. Ech significantly inhibited the migration/invasion and significantly increased the microfilament density in OVCAR-3 and HO-8910 cells, which was significantly related with the elasticity of the cells. An increase of elasticity and a decrease of invasion were found in OVCAR-3 and HO-8910 cells after Ech treatment. Together, this study clearly demonstrated the association of viscoelastic properties with the invasion of ovarian cancer cells and shed a light on the biomechanical changes for early diagnosis of tumor transformation and progression at single-cell level.

Highlights

Ovarian cancer is a lethal gynecological malignancy with low survival rates due to the fact that the disease is generally diagnosed during the late stages [1,2]
HBO1-directed histone H4 specific acetylation, potentiating the membrane elasticity of ovarian cancer cells, and HBO1 mRNA expression were significantly higher in OVCAR-3 cells than in the human ovarian surface epithelial cell (HOSEpiC) control [33]
The changes of average elasticity and cell invasion were analyzed after exposure to Ech (Figure 8) and the results showed no obvious changes of average elasticity (Figure 8a) and cell invasion (Figure 8c) in HOSEpiC cells, while there was a significant increase in OVCAR-3 and HO-8910 cells after Ech treatment (Figure 8a,c)

Summary

Introduction

Ovarian cancer is a lethal gynecological malignancy with low survival rates due to the fact that the disease is generally diagnosed during the late stages [1,2]. The present study examined the elasticity and viscosity through AFM, and cell migration, invasion and microfilament density through cell experiments, and the relationship between them was established. In order to determine the relationship between viscoelastic and tumorigenic properties of ovarian cancer cells, the present study further examined the migration and invasion changes of these cells besides the microfilament density of F-actin cytoskeleton.

Results

Conclusion