Expression of glycolytic enzymes is increased in pancreatic cancerous tissues as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry

Mikuriya, Kuniko; Kuramitsu, Yasuhiro; Ryozawa, Shomei; Fujimoto, Masanori; Mori, Sayaka; Oka, M.; Hamano, Kimikazu; Okita, Kiwamu; Sakaida, Isao; Nakamura, Kazuyuki

doi:10.3892/ijo.30.4.849

Cited by 87 publications

(95 citation statements)

References 40 publications

(41 reference statements)

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“…α-enolase is a plasminogen-binding protein and also appears to play a major role in the promotion of plasminogen activation by leukocytic cells [74]. Peptidylprolyl isomerase (cyclophilin A) has been associated with a number of cancer histiotypes including breast [75] and pancrease [76,77], and has been implicated in cellular resistance to hypoxia-and Cisplatininduced cell death [78] and resistance to aplidin [79]. Its secretion from regressive tumor masses has been previously been studied by MS [80] and it has been profiled as one of a number of glycolytic enzymes increased in pancreatic cancerous tissues [76].…”

Section: Non-classical Secretionmentioning

confidence: 99%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

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Proteins secreted (the secretome) from cancer cells are potentially useful as biomarkers of the disease. Using LC-MS/MS, the secreted proteomes from a series of isogenic breast cancer cell lines varying in aggressiveness were analyzed by mass spectrometry: non-tumorigenic MCF10A, premalignant/ tumorigenic MCF10AT, tumorigenic/locally invasive MCF10 DCIS.com and tumorigenic/ metastatic MCF 10CA cl. D. Proteomes were obtained from conditioned serum-free media, partially fractionated using a small reverse phase C2 column and digested with trypsin for analysis by LC-MS/MS, using a method previously shown to give highly enriched secreted proteomes (Mbeunkui, et. al., J. Prot. Res. 5, 899-906 2006). The search files produced from 5 analyses (3 separate preparations) were combined for database searching (Mascot) which produced a list of over 250 proteins from each cell line. The aim was to discover highly secreted proteins which changed significantly in abundance corresponding with aggressiveness. The most apparent changes were observed for alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted proteins from MCF10 DCIS.com and MCF10CA cl. D, yet undetected in the MCF10A and MCF10AT cell lines. Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D and lysyl oxidase. The S100 proteins, often associated with metastasis, showed variable changes in abundance. While the cytosolic proteins were low (e.g. actin and tubulin), there was significant secretion of proteins often associated with the cytoplasm. These proteins were all predicted as products of non-classical secretion (SecretomeIP, Center for Biological Sequence Analysis). The LC-MS/MS results were verified for five selected proteins by western blot analysis, and the relevance of other significant proteins is discussed. Comparisons with two other aggressive breast cancer cell lines are included and the protein with consistent association with aggressiveness in all lines, and in unrelated cancer cells, was the galectin-3-binding protein which has been associated with breast, prostate and colon cancer earlier, supporting the approach and findings. This analysis of an isogenic series of cell lines suggests the potential usefulness of the secretome for identifying prospective markers for the early detection and aggressiveness/progression of cancer.

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Section: Non-classical Secretionmentioning

confidence: 99%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

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“…We have previously demonstrated that TAGLN contributes to the enhanced migration of hypoxic human pulmonary artery smooth muscle cells (hPASMCs) (10). In addition, TAGLN overexpression has been observed in gastric malignancies (11,12) and pancreatic cancer (13). Such…”

Section: Introductionmentioning

confidence: 99%

Transgelin overexpression in lung adenocarcinoma is associated with tumor progression

Dong

Zhang

et al. 2014

International Journal of Molecular Medicine

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Abstract. Hypoxia is a common feature of solid tumors and is associated with an increased likelihood of local recurrence and distant metastasis. Transgelin (TAGLN) is an actin crosslinking/polymerization protein that belongs to the family of actin-associated proteins, and there is evidence that TAGLN may be involved in the migration of epithelial cells by interacting with actin or promoting podosome formation. Cell migration is a key step of cancer metastatis. Thus, the aim of this study was to investigate the potential link between TAGLN protein levels and hypoxia in lung adenocarcinoma cells and to explore the possible functions and expression patterns of TAGLN in lung adenocarcinoma. We first examined the effects of altered TAGLN expression on cell migration under both normoxic and hypoxic conditions. Immunohistochemical (IHC) staining was also performed to examine TAGLN protein expression patterns in lung adenocarcinoma samples. Our results revealed that TAGLN was upregulated in the hypoxic lung adenocarcinoma cells. The inhibition of TAGLN expression in the cells using small interfering RNA (siRNA) led to a decreased migration ability. TAGLN was significantly overexpressed in the lung adenocarcinoma tissues compared to the adjacent tumor-free tissues. A high TAGLN expression correlated with an advanced TNM stage, lymph node metastasis and greater differentiation. TAGLN was upregulated in the human lung adenocarcinoma cell lines under hypoxic conditions, which contributed to the migration ability of the cells. Thus, our data suggest that TAGLN may be a viable therapeutic target and a potential biomarker for predicting the prognosis of patients with lung adenocarcinoma.

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“…Over-expression of enzymes involved in the glycolytic pathway is a common feature of cancerous tissues. Increased glycolysis in cancer cells has been regarded as the result of intratumoral hypoxia and is possibly associated with tumor invasion, metastasis or resistance to therapy (37). As reported previously, GPDM participates in the reoxidation of cytosolic NADH by delivering reducing equivalents from this molecule into the electron transport chain, thus sustaining glycolysis (38).…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide phosphoribosyltransferase and prostaglandin H2 synthase 2 are up-regulated in human pancreatic adenocarcinoma cells after stimulation with interleukin-1

Bauer

Venz²,

Junker³

et al. 2009

Int J Oncol

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Abstract. Human pancreatic cancer is today an almost incurable disease with a 5-year survival rate of <5%. Chronic inflammation in the tumor region is often associated with cancer progression. In pancreatic tumors, the pro-inflammatory cytokine IL-1 has been found to affect the development of chemoresistance in this cancer type. In a search for new therapeutic targets we investigated the effect of this proinflammatory mediator on pancreatic cancer protein expression. Therefore, the human pancreatic adenocarcinoma cell line Colo357 was subjected to proteomic analysis after stimulation with IL-1 using 2D gel electrophoresis and mass spectrometry. We detected 11 spots as being differentially expressed after stimulation with IL-1 representing 11 different proteins. Among them, nicotinamide phosphoribosyltransferase (NAMPT) and prostaglandin H 2 synthase 2 (PGHS-2) are crucial proteins whose expression in Colo357 is increased by IL-1. This study is the first one demonstrating an up-regulation of NAMPT in a tumor model for human pancreatic cancer. Several clinical trials using selective PGHS-2 or NAMPT inhibitors alone did not lead to an improvement in clinical outcome. Against the background of a high cardiovascular risk associated with PGHS-2-specific pharmacological inhibitors, we recommend a combinatory treatment with selective NAMPT and PGHS-2 inhibitors. This might overcome the limitations associated with PGHS-2 inhibitors since agents at low doses and with complementary mechanisms will be used. Such combined administration should positively affect the balance between risk and benefit in fighting the interplay of tumor-associated pancreatic inflammation and carcinogenesis in high-risk patients with pancreatic neoplasia. IntroductionPancreatic cancer is the fourth cause of cancer-related mortality in the USA and the sixth one in Europe with more than 250,000 patients estimated to die of the disease worldwide (1). This cancer entity is one of the most deadly of all malignancies with a death to incidence ratio approaching one making mortality rate a robust approximation of incidence for pancreatic cancer (2). The incidence of pancreatic cancer correlates with increasing age reaching a peak in the 65-75-years old age group (3). Approximately three-fourths of patients will die within one year of diagnosis and <5% survive up to 5 years after diagnosis (4). The poor outcome of pancreatic cancer is reflected by non-resectable primary lesions, locally advanced tumors, and a high metastatic potential (5). Since only a few patients benefit from classical adjuvant chemo-and radiotherapy, complete surgical resection is the superior treatment modality for patients with resectable disease. Unfortunately, the majority of pancreatic cancer patients present with locally advanced or metastatic tumors are not amenable for curative surgery. Only a disappointing 15% of patients at the time of diagnosis are eligible to undergo surgical excision, and even patients who have undergone such curative resection often die of recurrent carcin...

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Expression of glycolytic enzymes is increased in pancreatic cancerous tissues as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry

Cited by 87 publications

References 40 publications

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

Transgelin overexpression in lung adenocarcinoma is associated with tumor progression

Nicotinamide phosphoribosyltransferase and prostaglandin H2 synthase 2 are up-regulated in human pancreatic adenocarcinoma cells after stimulation with interleukin-1

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