Construction of oral cancer microenvironment model using 3D culture technology and search for new therapeutic targets

Abstract

There remains much to be discovered and understood about the subtypes of cancer associated-fibroblasts (CAFs) in oral cancer. At the Faculty of Dentistry, Niigata University in Japan, Dr Kenta Haga is investigating the tumour microenvironment and CAFs. To do this, he and his team are using 3D culture technology in their studies as 3D culture models are considered to be more useful and more faithful to the biological characteristics and drug resistance of cancer than 2D cultures. This is because cells are never in 2D in the human body; they are all placed in a 3D structural environment. In their latest study, the researchers utilised their experimental model to recreate the cancer microenvironment and evaluate the proliferation and invasion of cancer cells over time. They have incorporated CAFs into a collagen gel, seeded oral cancer cells and established the basic technology for a 3D culture model with a two-layered structure that has a tumour layer and an interstitial layer to mimic squamous cell carcinoma. The team has been able to investigate the interaction of CAFs with oral cancer cells by in vitro, in vivo and in human oral cancer specimens. In order to understand the complex tumour microenvironment they are seeking to analyse the effects of CAFs on the invasive and proliferative potential for cancer cells. If they can elucidate the intercellular network in the tumour microenvironment, this will lead to novel treatment strategies for cancer. Haga and the team have already demonstrated that the TGF-β/SOX9 pathway plays an important role in CAFs promoting epithelial mesenchymal transition (EMT) in oral cancer.