Candidate Serological Biomarkers for Cancer Identified from the Secretomes of 23 Cancer Cell Lines and the Human Protein Atlas

Wu, Chih‐Ching; Hsu, Chia-Wei; Chen, Chi-De; Yu, Chia‐Jung; Chang, Kai‐Ping; Tai, Dar‐In; Liu, Hao‐Ping; Su, Wen-Hui; Chang, Yu‐Sun

doi:10.1074/mcp.m900398-mcp200

Cited by 183 publications

(220 citation statements)

References 93 publications

(112 reference statements)

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“…Analyses of the complete set of secreted proteins -otherwise known as the "secretome" -have been reported in various organisms, cell types, and pathologies, and are quickly gaining popularity [6,7]. Not surprisingly, several studies have focused on analyses of cancer-or metastasis-specific changes in secretome profiles [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, none of the studies to date has focused on secretomes relevant to the bone metastasis phenotype.…”

Section: Introductionmentioning

confidence: 99%

Global secretome analysis identifies novel mediators of bone metastasis

et al. 2012

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Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Global secretome analysis identifies novel mediators of bone metastasis

et al. 2012

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“…However, it is also evident that an important limitation of these systems is that observations made with experimental animal models cannot always be transferred to humans, a fact possibly due to the difference of brush border enzyme expression and its regulation by hormones and growth factors and the fundamental differences between animal and human tissues in the composition of the epithelial basement membrane along the crypt-villus axis (13). The application of human cancer cell lines such as Caco-2, HT29 and T84, which can undergo a spontaneous and complete intestinal-like program of differentiation (14,15), has been limited by their cancerous nature (11). Caco-2, which presents obvious limitations because of the neoplastic origin of the cells, is particularly unsuitable for studies on the regulatory factors that influence normal intestinal functions.…”

Section: Introductionmentioning

confidence: 99%

Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

Liu

Zhang

Zhou

et al. 2010

Braz J Med Biol Res

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Epithelium, a highly dynamic system, plays a key role in the homeostasis of the intestine. However, thus far a human intestinal epithelial cell line has not been established in many countries. Fetal tissue was selected to generate viable cell cultures for its sterile condition, effective generation, and differentiated character. The purpose of the present study was to culture human intestinal epithelial cells by a relatively simple method. Thermolysin was added to improve the yield of epithelial cells, while endothelin-3 was added to stimulate their growth. By adding endothelin-3, the achievement ratio (viable cell cultures/total cultures) was enhanced to 60% of a total of 10 cultures (initiated from 8 distinct fetal small intestines), allowing the generation of viable epithelial cell cultures. Western blot, real-time PCR and immunofluorescent staining showed that cytokeratins 8, 18 and mouse intestinal mucosa-1/39 had high expression levels in human intestinal epithelial cells. Differentiated markers such as sucrase-isomaltase, aminopeptidase N and dipeptidylpeptidase IV also showed high expression levels in human intestinal epithelial cells. Differentiated human intestinal epithelial cells, with the expression of surface markers (cytokeratins 8, 18 and mouse intestinal mucosa-1/39) and secretion of cytokines (sucrase-isomaltase, aminopeptidase N and dipeptidylpeptidase IV), may be cultured by the thermolysin and endothelin-3 method and maintained for at least 20 passages. This is relatively simple, requiring no sophisticated techniques or instruments, and may have a number of varied applications.

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“…Their descriptions and positions on gels are displayed in Table 1 and Figure 1. Other proteins, which were essentially related to cell membrane/membrane-bound or common to those in prior publications on cancer cell secretome [3], are listed in Table 2 (Supplementary File 1).…”

Section: Resultsmentioning

confidence: 99%

“…To overcome this drawback, proteomic identification of conditioned media of cancer cell lines has recently attracted much attention [1][2][3]. Generally, the identified proteins were already known to be involved in cancer development and progression, and subsequent studies validated the presence of several of them in sera from cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…The identification of cancer cell secretome has uncovered mechanisms related to angiogenesis, invasion and metastasis, and can contribute to the development of new strategies for the efficient control of cancer. Moreover, secreted or shed proteins can reach body fluids including serum, an ideal sample source for early diagnosis and monitoring of cancer [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

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Secretomic analysis of large cell lung cancer cell lines using two-dimensional gel electrophoresis coupled to mass spectrometry

Yousefi¹,

Sarvari²,

Nakamura³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The secretome of cancer cells is a valuable source of biomarkers that can ultimately reach the serum or other body fluids. Cancer biomarkers can facilitate early diagnosis and monitoring of the disease, contribute to our understanding of tumor biology, and support the development of more efficient therapies. Recently, high-throughput proteomic analysis of the conditioned media of cancer cell lines has shown potential to identify novel biomarkers in cancer. We used two-dimensional gel electrophoresis coupled to liquid chromatography tandem mass spectrometry to identify the secretome of the large cell lung cancer cell lines QU-DB and Mehr-80, which were established from a Canadian and a Persian patient, respectively. A total of 130 distinct protein species were identified. Most of them were previously found in serum or other body fluids, the membrane compartment or conditioned media of other cancer cell lines. Some of the proteins that we identified, e.g. IL-6, triosephosphate isomerase, PGP9.5, a-enolase, Dickkopf-1, and peroxiredoxin-1 have been already known as putative serum markers for lung cancer, whereas others might be candidate markers for further validation in lung cancer body fluids such as IL-25, stathmin, vimentin, peptidyl-prolyl cis-trans isomerase A, transgelin-2, and chloride intracellular channel protein 4.

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Candidate Serological Biomarkers for Cancer Identified from the Secretomes of 23 Cancer Cell Lines and the Human Protein Atlas

Cited by 183 publications

References 93 publications

Global secretome analysis identifies novel mediators of bone metastasis

Global secretome analysis identifies novel mediators of bone metastasis

Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

Secretomic analysis of large cell lung cancer cell lines using two-dimensional gel electrophoresis coupled to mass spectrometry

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