In Vitro Reconstruction of Brain Tumor Microenvironment
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Review Article
In Vitro Reconstruction of Brain Tumor Microenvironment Ilkyoo Koh1 & Pilnam Kim
1,
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Received: 27 November, 2018 / Accepted: 10 January, 2019 / Published online: 06 March, 2019 â’¸The Korean BioChip Society and Springer 2019
Abstract The cancer cells in brain tumors interact with their microenvironment, which includes stromal cells, the extracellular matrix (ECM), and the physical properties of tissues. The reciprocal interaction between cancer cells and the surrounding microenvironment regulates the biological behavior of cancer cells. To improve our understanding of the progression of brain tumors, it is useful to construct physiologically relevant brain tumor models. Consequently, versatile in vitro tumor models ranging from simplistic twodimensional (2D) cultures to three-dimensional (3D) cultures have been developed to mimic the microenvironments of the brain. This review covers the recent progress in the in vitro reconstruction of brain tumor microenvironments. Keywords: Brain tumor, Microenvironment, In vitro model
Introduction A brain tumor is a growth of abnormal cells in the brain tissues that multiply in an uncontrolled manner. Clinically, the World Health Organization (WHO) classifies brain tumors into four grades according to histological and molecular parameters.1 Grades I and II are benign tumors that grow slowly and are the least aggressive. Malignant, high-grade (grades III and IV) brain tumors grow rapidly and consist of abnormalappearing cells that infiltrate the surrounding tissues and have a poor prognosis.2 The standard treatments 1 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea *Correspondence and requests for materials should be addressed to Pilnam Kim ( [email protected])
for brain tumors are surgical resection, radiotherapy, and chemotherapy with alkylating agents.3 However, these therapies focus on inhibition of the neoplasm or proliferating cells, and not on the cells infiltrating the brain.4,5 Therefore, these conventional therapies lack efficacy in most high-grade brain tumors and the patients have poor outcomes or develop recurrent tumors. To enhance treatment effectiveness and predict the prognosis, it is important to understand the characteristics of brain tumors, including their growth and invasion. The brain tumor microenvironment, including blood vessels, immune cells, inflammatory cells, signaling molecules, and the extracellular matrix (ECM), can regulate tumor progression by interacting directly with cancer cells.6-8 Brain tissues have unique microenvironments that distinguish them from other tissues with low stiffness and loosely connected cellular network,9 including the composition of the ECM, anatomical structures, and specialized cell types, such as neurons, astrocytes, and microglia. The ECM component of brain tissue contains high amounts of hyaluronic acid (HA), glycosaminoglycans (GAGs), and proteoglycans, but lacks fibrous materials such as collagen, fibronectin,
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