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Wang Y.,Shandong University | Wang Y.,Qingdao University | Wang Y.,Key Laboratory of Urinary System Diseases | Zhao Y.,Qingdao University | And 10 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2017

The tumor microenvironment, which is composed of tumor cells and non-malignant cells, plays a crucial role in malignant transformation, local invasion, distant metastasis and drug resistance. Reconstructing the tumor microenvironment in vitro has been used as an indispensable strategy to elucidate the mechanism of tumorigenesis, provide an early diagnosis and screen drugs. In the past few decades, several simulation platforms have been developed, including spontaneous cell aggregation, cellular scaffolding, the multicellular tumor spheroid model (MCTS), the rotary cell culture system (RCCS), and microfluidic devices. Using these systems, researchers have made significant progress in understanding the regulatory mechanisms of the tumor microenvironment and also in clinical research. These platforms can increase research efficiency, can help achieve individualized diagnoses and treatments and allow for high-throughput drug screening. In this review, we will introduce the current status of tumor microenvironment simulation platforms and their advantages and disadvantages. In addition, we further discuss their applications in their early clinical diagnosis and high-throughput screening of drugs, and their challenges and prospects in the future will be addressed.

Shi H.,Qingdao University | Shi H.,Key Laboratory of Urinary System Diseases | Jiang H.,Qingdao University | Wang L.,Qingdao University | And 11 more authors.
Cell Cycle | Year: 2015

Stromal fibroblasts are essential for tumor proliferation and invasion. Here we presented a 3-dimensional (3D) microfluidic co-culture device to reconstruct an in vivo-like tumor microenvironment for investigation of the interactions of cancer-associated fibroblasts (CAFs) and bladder cancer cells. With this device, we verified that the cytokines secreted by bladder cancer cells T24 effectively transform the fibroblasts into CAFs. Compared to fibroblasts, the CAFs, which undergo the aerobic glycolysis, showed higher ability to produce lactate and provide energy for bladder cancer cell proliferation and invasion. We also demonstrated that this kind of tumor-promoting effect was associated with the upregulation of monocarboxylate anion transporter 1 (MCT1) and MCT4 expression in CAFs. We concluded that MCT1 and MCT4 are involved in bladder cancer cell proliferation and invasiveness. Moreover, this 3D microfluidic co-culture device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment. © 2015 Taylor & Francis Group, LLC.

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