Reconstituting Glioma Perivascular Niches on a Chip for Insights into Chemoresistance of Glioma

Lin, Caihou; Li, Gang; Mao, Sifeng; Yang, Lijuan; Yi, Linglu; Lin, Xuexia; Wang, Junming; Zhang, Lin; Lin, Jin‐Ming

doi:10.1021/acs.analchem.8b02133

Cited by 35 publications

(44 citation statements)

References 34 publications

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“…In normal brain, most of CHIP protein was expressed in the cytoplasm of neurons. Moreover, CHIP is a key regulator of glioma progression, as evident by the fact that ChIP overexpression can promote the colony formation and proliferation of glioma cell lines in vitro, while CHIP knockdown can achieve the opposite result; and a consistent result was obtained by in vivo experiment 26 . These results indicate that CHIP is necessary for tumorigenesis and can induce the tumorigenesis of human glioma.…”

Section: Discussionmentioning

confidence: 56%

“…Moreover, CHIP is a key regulator of glioma progression, as evident by the fact that ChIP overexpression can promote the colony formation and proliferation of glioma cell lines in vitro, while CHIP knockdown can achieve the opposite result; and a consistent result was obtained by in vivo experiment. 26 These results indicate that CHIP is necessary for tumorigenesis and can induce the tumorigenesis of human glioma. However, it has been found that CHIP has the characteristics of oncogene in some tumors, and it can also play the role of tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 85%

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Carboxy terminus of HSP70‐interacting protein (CHIP) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability

Dang

et al. 2020

Environmental Toxicology

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Cancer cell stemness results in the occurrence and progression of tumors and Oct4 (octamer‐binding transcription factor) has been confirmed to be a critical contributor and marker of cancer cell stemness. Here, we aimed to explore the underlying mechanisms contributing to Oct4 protein stability, which is necessary for thyroid cancer (TC) cell stemness. We indicated that carboxy terminus of HSP70‐interacting protein (CHIP) protein was lowly expressed in TC tissues and cells, and positively correlated with the overall survival of TC patients. By analyzing the co‐expression network in TC tissues, we found that CHIP and Oct4 expression exhibited a negative correlation. Functional experiments showed that CHIP knockdown promoted the stemness of TC cells, while CHIP overexpression reduced the stemness of TC spheroids formed by TC cells, in which CHIP expression was significantly decreased. Furthermore, CHIP had no effect on TC cell viability. Mechanistic studies revealed that CHIP directly interacted with Oct4 protein and induced Oct4 ubiquitination, whereas a catalytic CHIP mutant (H260Q) did not. And CHIP regulated the stemness of TC cells in an Oct4‐dependent manner. Overall, this work indicates that the CHIP/Oct4 axis is essential for TC cell stemness.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 85%

Carboxy terminus of HSP70‐interacting protein (CHIP) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability

Dang

et al. 2020

Environmental Toxicology

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“…Lin et al elucidated that endothelial cells in the perivascular microenvironment promote resistance to drug response of glioma stem cells (GSC), which was challenging to show in conventional 2D culture environments that do not recapitulate interactions of endothelial cells and glioma cells [ 46 ]. Accordingly, GSCs could be treated in the nature-mimicking glioma PVN on the microdevice while maintaining cancer stem cells at the multipotent status owing to cell-cell communications.…”

Section: Glioma-on-chip Platformsmentioning

confidence: 99%

“…In the case of treatment of the GSCs by TMZ, 7-methylguanine (7-MeG) and 6-O-methylguanine (6-O-MeG) are the two biomarkers of chemoresistance diagnosis [ 22 ]. Using the proposed OOC platform, the expression levels of 7-MeG and 6-O-MeG culture were observed to be higher than cocultured GSCs, highlighting the role of endothelial cells in chemoresistance and glioma therapies [ 46 ].…”

Section: Glioma-on-chip Platformsmentioning

confidence: 99%

Glioma-on-a-Chip Models

et al. 2021

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Glioma, as an aggressive type of cancer, accounts for virtually 80% of malignant brain tumors. Despite advances in therapeutic approaches, the long-term survival of glioma patients is poor (it is usually fatal within 12–14 months). Glioma-on-chip platforms, with continuous perfusion, mimic in vivo metabolic functions of cancer cells for analytical purposes. This offers an unprecedented opportunity for understanding the underlying reasons that arise glioma, determining the most effective radiotherapy approach, testing different drug combinations, and screening conceivable side effects of drugs on other organs. Glioma-on-chip technologies can ultimately enhance the efficacy of treatments, promote the survival rate of patients, and pave a path for personalized medicine. In this perspective paper, we briefly review the latest developments of glioma-on-chip technologies, such as therapy applications, drug screening, and cell behavior studies, and discuss the current challenges as well as future research directions in this field.

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“…Chemoresistance of glioma was studied by analyzing the metabolism of temozolomide in an artificial glioma perivascular niche. 99 Chemoresistance of temozolomide on glioma stem cells and the molecular metabolism was investigated by an ESI-MS. Microfluidic chips provide a simulated microenvironment for cells, while MS provides the possibility for high-throughput detection. Metabolism and its kinetic of 8 drugs are evaluated, by coupling of a liver chip and MS. Hepatic clearances were extrapolated on this strategy.…”

Section: Drug Screeningmentioning

confidence: 99%

Cell Analysis on Microfluidics Combined with Mass Spectrometry

Zhang

Lin

2020

ANAL. SCI.

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Cell analysis is of great significance for the exploration of human diseases and health. However, there are not many techniques for high-throughput cell analysis in the simulated cell microenvironment. The high designability of the microfluidic chip enables multiple kinds of cells to be co-cultured on the chip, with other functions such as sample preprocessing and cell manipulation. Mass spectrometer (MS) can detect a large number of biomolecules without labelling. Therefore, microfluidic chip coupled with MS has been a major branch of cell analysis during the past decades. Here, we concisely introduce various microfluidic devices coupling with MS used for cell analysis. The main functions of microfluidic devices were first described, followed with different interfaces to different types of MS. Then, their various applications in cell analysis were highlighted, with an emphasis on cell metabolism, drug screening, and signal transduction. Current limitations and prospective trends of microfluidics coupling with MS are discussed at the end.

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Reconstituting Glioma Perivascular Niches on a Chip for Insights into Chemoresistance of Glioma

Cited by 35 publications

References 34 publications

Carboxy terminus of HSP70‐interacting protein (CHIP) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability

Carboxy terminus of HSP70‐interacting protein (CHIP) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability

Glioma-on-a-Chip Models

Cell Analysis on Microfluidics Combined with Mass Spectrometry

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