Membrane proteomic analysis comparing squamous cell lung cancer tissue and tumour-adjacent normal tissue

Li, Burong; Chang, Jiantong; Chu, Yangyang; Kang, Huafeng; Yang, Jun; Jiang, Jiantao; Ma, Hongbin

doi:10.1016/j.canlet.2011.12.037

Cited by 17 publications

(10 citation statements)

References 18 publications

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“…1 ). One of the possible explanations of such a difference may be associated with a different membrane protein composition in normal and cancer cells 17 . It may influence not only on the pathogenicity of tumour cells but also distinct sensitivity to cytotoxic or antifungal drugs.…”

Section: Discussionmentioning

confidence: 99%

Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals the mechanisms associated with the drug toxicity and cell defence

Grela

Pięt

Luchowski

et al. 2018

Sci Rep

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Amphotericin B is an antibiotic used in pharmacotherapy of life-threatening mycotic infections. Unfortunately, the applicability of this antibiotic is associated with highly toxic side effects. In order to understand molecular mechanisms underlying toxicity of amphotericin B to patients, two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of the drug and imaged with the application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. The results of the cell viability assays confirm high toxicity of amphotericin B towards human cells. The images recorded demonstrate effective binding of amphotericin B to biomembranes. Analysis of the images reveals the operation of a defence mechanism based upon the elimination of molecules of the drug from living cells via formation of small amphotericin B-containing lipid vesicles. The fact that exosomes formed are devoid of cholesterol, as concluded on the basis of the results of Raman analysis, suggests that sequestration of sterols from the lipid phase of biomembranes is not a sole mechanism responsible for the toxic side effects of amphotericin B. Alternatively, the results imply that molecules of the drug present directly within the hydrophobic membrane core disturb the lipid membrane structure and affect their biological functions.

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Section: Discussionmentioning

confidence: 99%

Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals the mechanisms associated with the drug toxicity and cell defence

Grela

Pięt

Luchowski

et al. 2018

Sci Rep

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“…Although initial use of platin-based cytotoxic chemotherapy improved the overall survival rate and life quality of the patients, the outcome remains poor due to deleterious development of drug resistance resulting in less than 15% lung cancer patients surviving for at least five years [2,3]. Approximately 80 - 85% of the lung cancer patients are diagnosed with an advanced stage of non-small cell lung cancer (NSCLC) that has limited therapeutic options due to metastasis [1,4,5] and among the three types of NSCLC, patients identified with squamous carcinoma which involves lymph node metastasis accounts for 60% [5,6].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Raf-MEK-ERK and Hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line

Lee

Jaganath

Manikam

et al. 2013

BMC Complement Altern Med

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BackgroundLung cancer constitutes one of the malignancies with the greatest incidence and mortality rates with 1.6 million new cases and 1.4 million deaths each year. Prognosis remains poor due to deleterious development of multidrug resistance resulting in less than 15% lung cancer patients reaching five years survival. We have previously shown that Phyllanthus induced apoptosis in conjunction with its antimetastastic action. In the current study, we aimed to determine the signaling pathways utilized by Phyllanthus to exert its antimetastatic activities.MethodsCancer 10-pathway reporter array was performed to screen the pathways affected by Phyllanthus in lung carcinoma cell line (A549) to exert its antimetastatic effects. Results from this array were then confirmed with western blotting, cell cycle analysis, zymography technique, and cell based ELISA assay for human total iNOS. Two-dimensional gel electrophoresis was subsequently carried out to study the differential protein expressions in A549 after treatment with Phyllanthus.ResultsPhyllanthus was observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via suppression of Raf protein. Inhibition of this pathway resulted in the suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis. Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1α that led to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of proteins downregulated by Phyllanthus that were involved in metastatic processes, including invasion and mobility proteins (cytoskeletal proteins), transcriptional proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species tested, P. urinaria showed the greatest antimetastatic activity.ConclusionsPhyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways that led to suppression of various critical proteins for A549 invasion and migration.

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“…Other approaches such as proteomics and transcriptional sequencing may find other potential cancer markers. For example, proteomics approaches have been successfully applied toward the identification of membrane-associated proteins in lung tumor tissue relative to normal lung tissue [ 84 , 85 ]. Nonetheless we have identified a suite of 10 potential cell-surface markers that identify the majority of lung tumor samples we analyzed.…”

Section: Discussionmentioning

confidence: 99%

Cell-surface marker discovery for lung cancer

et al. 2017

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Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients.

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Membrane proteomic analysis comparing squamous cell lung cancer tissue and tumour-adjacent normal tissue

Cited by 17 publications

References 18 publications

Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals the mechanisms associated with the drug toxicity and cell defence

Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals the mechanisms associated with the drug toxicity and cell defence

Inhibition of Raf-MEK-ERK and Hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line

Cell-surface marker discovery for lung cancer

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