The Unequal Mechanical Force Drives Glioma-macrophage Spheroid Formation

Megha Jhunjhunwala¹, Rong-Shing Chang¹, Yujia Cui¹, Chi-Shuo Chen^1*

¹Dept of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

* Presenter:Chi-Shuo Chen, email:chen.cs@mx.nthu.edu.tw

High-grade glioma is frequently accompanied with tumor-associated macrophages (TAM) infiltration, and the prognosis of the patient is about only 2-5 years. During the glioma development, in addition to TAM infiltrate into the solid tumor, glioma progress with the intracranial pressure increasing. In this study, from the perspective of biophysics, we utilize the grade III astrocytoma and the CNS resident macrophage cell lines as the study model, to investigate the mechanosignal transmission in TAM-glioma structure assembly. We notice that the physical contacts between macrophages and glioma are essential for tumor spheroid formation. By measuring intercellular traction force, a tug-of-war model was established to interpret the imbalanced traction force in the 3-dimensional TAM-glioma spheroid formation. The quantitative mRNA results indicated gap junctions are associated with tumor formation progress. Engineered hydrogels with various physiological stiffness are also utilized to modulate the TAM-glioma interactions, and the results implied that the soft microenvironment and TAM infiltration can contribute to the formation of 3-dimensional TAM-glioma cell architecture. Our results demonstrated mechanosignals may play essential roles in brain tumor formation, and the findings are expected to contribute to our understanding about tumor progression.

Keywords: cellular traction force, physical microenvironment, glioma, tumor-associated macrophages