The softening of human bladder cancer cells happens at an early stage of the malignancy process.

Jorge R Ramos,Joanna Pabijan,Malgorzata Lekka,Ricardo Garcia

doi:10.3762/bjnano.5.52

Abstract

Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young’s modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force.

Highlights

During oncogenic progression, many cancer-related alterations change both the internal structures of cells and their surroundings, i.e., the extracellular matrix (ECM)
The atomic force microscopy (AFM) error image shows that these filaments are organized in two groups: (i) short actin filaments and (ii) and bundles of long acting filaments
The other types of malignant cells, HTB-9 and HT-1376 do not show the presence of stress fibers. These results are consistent with fluorescence microscopy images of actin filaments stained by using phalloidin that was labeled with Alexa Fluor 488 dye (Figure 2, panels D, H, L, P and Figure S1 in Supporting Information File 1)

Summary

Introduction

Many cancer-related alterations change both the internal structures of cells and their surroundings, i.e., the extracellular matrix (ECM). The best example is breast cancer, whose solid tumors are detectable in macroscale by palpation whereas single cells show a larger deformability [3] In this context, it has been proposed that tumorigenesis in breast tissues is driven by changes in the mechanical properties of the extracellular matrix [2,4]. It has been proposed that tumorigenesis in breast tissues is driven by changes in the mechanical properties of the extracellular matrix [2,4] In this case the ECM of the malignant cells is stiffer (reflected by a higher Young’s modulus) as compared to the ECM of non-malignant tissues [2]. The relationship between mechanics at the cellular level and tumorigenesis represents a new perspective for which many issues need to be addressed

Results

Discussion

Conclusion