Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1)

Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S.; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P.

doi:10.1074/jbc.m115.639773

Cited by 29 publications

(31 citation statements)

References 37 publications

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“…The application of mass spectrometry analysis techniques to this biological model promises to provide new insight into cancer progression and treatment response. This includes identification of altered metabolism, cell–cell interactions and cell–ECM connections as well as antigen expression . Although additional techniques are required to complement proteomics analysis of these structures, it represents a powerful foundation from which novel cancer research can be developed.…”

Section: Resultsmentioning

confidence: 99%

“…This approach identified more than 823 ± 45 spots in monolayer culture and 762 ± 65 in MCTS with 73 of these spots shown to be significantly differentially abundant between the two groups. This was followed up with in‐gel tryptic digestion and LC‐MS/MS identifying a number of proteins involved in cytoskeletal organization and indicative of a shift toward anaerobic glycolysis, which has been widely observed in MCTS . The microenvironmental stresses on cancer, replicated through MCTS culture, are vital in the shift to glycolytic metabolism which mediates angiogenesis, tumor progression, and metastasis …”

Section: Analysis Techniques For Investigating Mctsmentioning

confidence: 99%

“…Additionally, a number of proteins involved in MCTS formation itself have been identified. For example, the importance of chloride channels in MCTS formation in ovarian cancer . Although mass spectrometry has been able to elucidate the altered abundance of proteins in these various MCTS contexts, further experiments are required to determine the biological relevance of these results.…”

Section: Analysis Techniques For Investigating Mctsmentioning

confidence: 99%

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Mass Spectrometry Analyses of Multicellular Tumor Spheroids

Acland

Mittal

Lokman

et al. 2018

Proteomics Clinical Apps

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Multicellular tumor spheroids (MCTS) are a powerful biological in vitro model, which closely mimics the 3D structure of primary avascularized tumors. Mass spectrometry (MS) has established itself as a powerful analytical tool, not only to better understand and describe the complex structure of MCTS, but also to monitor their response to cancer therapeutics. The first part of this review focuses on traditional mass spectrometry approaches with an emphasis on elucidating the molecular characteristics of these structures. Then the mass spectrometry imaging (MSI) approaches used to obtain spatially defined information from MCTS is described. Finally the analysis of primary spheroids, such as those present in ovarian cancer, and the great potential that mass spectrometry analysis of these structures has for improved understanding of cancer progression and for personalized in vitro therapeutic testing is discussed.

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Section: Resultsmentioning

confidence: 99%

Section: Analysis Techniques For Investigating Mctsmentioning

confidence: 99%

Section: Analysis Techniques For Investigating Mctsmentioning

confidence: 99%

See 1 more Smart Citation

Mass Spectrometry Analyses of Multicellular Tumor Spheroids

Acland

Mittal

Lokman

et al. 2018

Proteomics Clinical Apps

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“…24 Various techniques have been proposed for clustering cells and forming EBs. 14,25 Some studies have used the natural aggregation of cells on a substrate treated for adhesion. 25 However, this process requires several days to form aggregates.…”

Section: Introductionmentioning

confidence: 99%

Digital microfluidic platform for dielectrophoretic patterning of cells encapsulated in hydrogel droplets

et al. 2016

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In this article, we present a method for cell culture on a digital microfluidic (DMF) platform.Dielectrophoresis is used for trapping and patterning cells encapsulated within a 3D gelatin methacrylate (GelMA) hydrogel. In this method, planar traps are patterned within the electrodes on the DMF chip. Dispersed HEK 293 cells in GelMA solution are used to show negative dielectrophoresis when subject to a voltage at 20 kHz. The effects of the cell concentration, trap area, and trap spacing are analyzed. The rise time for patterning cells is shown to be rapid, from 8.5 seconds to 198.3 seconds for 50 mm and 500 mm diameter traps, respectively. The number of cells trapped was significantly influenced by the trap diameter and cell concentration. Live/dead assayed cells under a fluorescence microscope indicated that clusters of HEK 293 cells are 66% viable after 4 days of culturing. Certain trap designs were 78% viable on average after 4 days. This platform can be applied to execute quantitative, automated cell behavior studies and drug tests on the array of cells in vitro.

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“…In addition to other members of the Anoctamin family (Table 1) Amplification and overexpression of ANO1 in different cancerous tissues have been confirmed; however, there is no strong evidence on how cell proliferation and migration could be related to ANO1 overexpression. Antagonists of CaCCs can be investigated to see their therapeutic potentials via apoptosis of cancer cells as recently suggested in different studies (Guan, Song, Gao, Gao, & Wang, 2016;Jia, Liu, Guan, Lu, & Wang, 2015;Musrap et al, 2015). Furthermore, the crystallography studies in higher resolutions, in combination with bioinformatics approaches, can help us decipher the proper gating, voltage, and calcium sensitivity of these channels that can be of great value in designing novel therapeutic drugs.…”

Section: Caccs Dysregulation In Pathological Conditions and Potentimentioning

confidence: 99%

Molecular, biophysical, and pharmacological properties of calcium‐activated chloride channels

Kamaleddin

2017

Journal Cellular Physiology

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Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. They are mainly responsible for the movement of Cl and other anions across the biological membranes, and they are widely expressed in different tissues. Since the Cl flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca concentration on these channels is attracting a lot of attentions. After summarizing the molecular, biophysical, and pharmacological properties of CaCCs, the role of CaCCs in normal cellular functions will be discussed, and I will emphasize how dysregulation of CaCCs in pathological conditions can account for different diseases. A better understanding of CaCCs and a pivotal regulatory role of Ca can shed more light on the therapeutic strategies for different neurological disorders that arise from chloride dysregulation, such as asthma, cystic fibrosis, and neuropathic pain.

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Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1)

Cited by 29 publications

References 37 publications

Mass Spectrometry Analyses of Multicellular Tumor Spheroids

Mass Spectrometry Analyses of Multicellular Tumor Spheroids

Digital microfluidic platform for dielectrophoretic patterning of cells encapsulated in hydrogel droplets

Molecular, biophysical, and pharmacological properties of calcium‐activated chloride channels

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