The response of osteosarcoma cells to chemotherapeutic in presence of adipose stem cells: Pilot study in 3D

Chemotherapeutic resistance is a burning issue in long-term effective treatment of cancer. Hence deciphering the basis of cancer cell resistance has evident significance. The behavior of cancer cells is pre-dominantly regulated by different cells present in tumor-associated stroma, which confers the heterogeneity to tumor. Therefore, the investigation of role of individual cells in chemotherapeutic resistance needs to be unwound. Mesenchymal stem cells are actively recruited by tumor-associated stroma.¹ The present study aims to investigate the role of adipose derived mesenchymal stem cells (hASCs) on chemotherapeutic response of osteosarcoma. ASCs are widely used in clinical fields such as plastic surgery to promote the repair of target tissues. Nevertheless, the potential risk of using them in patient with cancer history needs to be assessed. Using 3D spheroid culture to mimic the spatial cellular organization and interactions of tumor niche,² it is observed that ASCs sequentially surrounded osteosarcoma cells in heterotypic culture, facilitating the cancer spheroid formation. When cultured in equal seeding ratio and treated with the model chemotherapeutic agent such as doxorubicin, the heterotypic culture exhibits different sensitivity compared to homotypic spheroid culture. Ongoing study includes the metabolic reprogramming of cancer cells, levels of secreted cytokines and gene analysis in heterotypic tumor stroma to anticipate the chemotherapeutic resistance.

Acknowledgement: This work is supported by the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement nº 668983 — FoReCaST. VM Correlo acknowledges Investigator FCT program (IF/01214/2014) and JM Oliveira to the program Investigador FCT2015 (IF/01285/2015).

References

1. Roodhart JML, Daenen LGM, Stigter ECA, et al. Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell 2011; 20:370–383. 
2. Rodrigues T, Kundu B, Silva-Correia J, Kundu SC, Oliveira JM, Reis RL, Correlo VM. Emerging tumor spheroids technologies for 3D in vitro cancer modeling. Pharmacol. Ther. 2018; 184:201-211.