Mechanical Property Changes in Breast Cancer Cells Induced by Stimulation with Macrophage Secretions in Vitro.

Hyonchol Kim,Tomoko Okada,Kenta Ishibashi,Chikashi Nakamura

doi:10.3390/mi10110738

Abstract

The contribution of secretions from tumor-associated macrophage (TAM)-like cells to the stimulation of mechanical property changes in murine breast cancer cells was studied using an in vitro model system. A murine breast cancer cell line (FP10SC2) was stimulated by adding macrophage (J774.2) cultivation medium containing stimulation molecules secreted from the macrophages, and changes in mechanical properties were compared before and after stimulation. As a result, cell elasticity decreased, degradation ability of the extracellular matrix increased, and the expression of plakoglobin was upregulated. These results indicate that cancer cell malignancy is upregulated by this stimulation. Moreover, changes in intercellular adhesion strengths between pairs of cancer cells were measured before and after stimulation using atomic force microscopy (AFM). The maximum force required to separate cells was increased by stimulation with the secreted factors. These results indicate the possibility that TAMs cause changes in the mechanical properties of cancer cells in tumor microenvironments, and in vitro measurements of mechanical property changes in cancer cells will be useful to study interactions between cells in tumor microenvironments.

Highlights

Tumor microenvironments are composed of various cells, including stromal cells, and play critical roles in tumor metastasis [1]
Tumor-associated macrophages (TAMs) in particular are considered to contribute to the upregulation of tumor malignancy [2,3,4], and pathological evidence has indicated that the abundance of tumor-associated macrophage (TAM) strongly correlates with poor prognosis [5,6,7]
FP10SC2 cells were stimulated for 1 day by adding MΦ-CM containing molecules secreted from TAM-like macrophages to the culture dish

Summary

Introduction

Tumor microenvironments are composed of various cells, including stromal cells, and play critical roles in tumor metastasis [1]. Despite the importance of interactive stimulation between TAMs and cancer cells for tumor development, the contribution of this stimulation to the regulation of cancer cell mechanical properties s remains poorly studied. We established an in vitro model of the macrophage stimulation of cancer cells as a mimic of the stimulation with tumor-conditioned medium [20,21]. Mechanical properties such as intercellular adhesion strength and cell elasticity were measured quantitatively and compared before and after stimulation to evaluate how the stimulation contributed to the regulation of cancer cell malignancy

Methods

Results

Discussion

Conclusion