Osteosarcoma tumor microenvironment relationship in 3D in vitro co-culture models

Microenvironment identifies cancer cells and non-cellular structure in the tumor tissue. Fibroblasts, immune cells, signaling molecules, extracellular matrix (ECM), connective tissue, integrins, and cytokines present in this environment. Microenvironment plays an active role in tumor angiogenesis, invasion and migration, drug resistance and tumor progression. Cytokines and chemokines contribute to tumor invasion-migration as much as phenotypic and genotypic changes. The aim of this study is to investigate effects of mesenchymal stem cell and normoxic and hypoxic conditions on tumor behavior in 3-dimensional (3D) in vitro cancer model mimicking in vivo tissue features best with creating different microenvironments. In this study, bone marrow-derived mesenchymal stem cells and osteosarcoma cells were cultured together in normoxic and hypoxic conditions, and micro-environment cross-talk was modeled in our laboratory. The invasion-migrationn rates were measured with xCELLigence DP (ACEA, Biosciences, San Diego, CA) real-time cell analysis system. The invasionmigration rates of cells in 3D co-culture was found to increase significantly compared to the two-dimensional. In addition, it has been shown that hypoxic conditions increase the migration and invasion of osteosarcoma cells compered to normoxic conditions, and this situation is triggered especially in 3D culture. Prognostic evaluation of patients with OS is limited to clinical parameters and molecular markers of tumor agressiveness effecting metastasis can't be defined accurately. At this point, 3D co-culture studies has been shown to reflect in vivo tumor structure and microenvironment relationships better. However, dynamism and components of tumor microenvironment should be analysed for detection of critical parameters independent of OS subtypes.