Comprehensive Analysis of Conditioned Media from Ovarian Cancer Cell Lines Identifies Novel Candidate Markers of Epithelial Ovarian Cancer

Gunawardana, C. Geeth; Kuk, Cynthia; Smith, Chris; Batruch, Ihor; Soosaipillai, Antoninus; Diamandis, Eleftherios P.

doi:10.1021/pr900411g

Cited by 73 publications

(79 citation statements)

References 42 publications

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“…Despite the relatively small number of tissue and ascites specimens studied, the majority of proteins identified in the present study as being significantly differentially secreted from malignant and CTRL cell samples had been detected in previous studies (8)(9)(10)(11)(12)(13)(14)(15)(16), confirming their potent and important role. To the best of our knowledge, proteins including HSP-10 and DKK3, had not previously been identified by a proteomic approach, but had been suggested as potent markers using alternate approaches (19,30); however the present study was unable to confirm their utility as biomarkers of serous ovarian cancer by the immunological method.…”

Section: Discussionsupporting

confidence: 76%

“…Although in vitro culture conditions may not fully reflect the in vivo conditions, identification of ovarian proteins differentially secreted by malignant cells may be a first step towards the elucidation of ovarian cancer markers in blood samples. In this context, secretome analysis of ovarian cancer cell lines has contributed to the establishment of a list of potent biomarkers (11,15,16). However, the pathological relevance of the cell line secretome is debatable.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of the ovarian cancer cell line secretome has also provided information on potential markers (11,15). However, these studies were based on cancer cell line comparison analyses, and the in vivo physiological and pathological relevance was questionable.…”

Section: Introductionmentioning

confidence: 99%

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Comparative secretome of ovarian serous carcinoma: Gelsolin in the spotlight

et al. 2017

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Abstract. Ovarian cancer is one of the most common types of reproductive cancer, and has the highest mortality rate amongst gynecological cancer subtypes. The majority of ovarian cancers are diagnosed at an advanced stage, resulting in a five-year survival rate of ~30%. Early diagnosis of ovarian cancer has improved the five-year survival rate to ≥90%, thus the current imperative requirement is to identify biomarkers that would allow the early detection, diagnosis and monitoring of the progression of the disease, or of novel targets for therapy. In the present study, secreted proteins from purified ovarian control, benign and cancer cells were investigated by mass spectrometry, in order to identify novel specific markers that are easy to quantify in patients sera. A total of nine proteins revealed significant differential secretion from control and benign cells, in comparison with ovarian cancer cells. The mRNA expression levels of three of these proteins (Dickkopf protein 3, heat shock protein 10 kDa and gelsolin) were subsequently evaluated by reverse transcription-quantitative polymerase chain reaction. Combined with the protein level in serum, the present study identified that gelsolin may be a useful marker of ovarian cancer.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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Comparative secretome of ovarian serous carcinoma: Gelsolin in the spotlight

et al. 2017

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“…Cancer cell line secretomes offer a valuable alternative to serum or plasma for the discovery of potential biomarkers, and have been used as a source for discovery of secreted biomarkers for prostate, ovarian, lung, and other tumors (3,(11)(12)(13)(14)(15)(16). The cancer cell secretome is composed of proteins secreted or shed by tumor cells in culture and detected in the serum-free conditioned media (CM).…”

Section: Head and Neck Squamous Cell Carcinoma (Hnscc)mentioning

confidence: 99%

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Sepiashvili

Hui

Ignatchenko

et al. 2012

Molecular & Cellular Proteomics

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Head and neck squamous cell carcinomas (HNSCC) can arise from the oral cavity, oropharynx, larynx or hypopharynx, and is the sixth leading cancer by incidence worldwide. The 5-year survival rate of HNSCC patients remains static at 40 -60%. Hence, biomarkers which can improve detection of HNSCC or early recurrences should improve clinical outcome. Mass spectrometry-based proteomics methods have emerged as promising approaches for biomarker discovery. As one approach, mass-spectrometric identification of proteins shed or secreted from cancer cells can contribute to the identification of potential biomarkers for HNSCC and our understanding of tumor behavior. In the current study, mass spectrometry-based proteomic profiling was performed on the conditioned media (i.e. secretome) of head and neck cancer (HNC) cell lines (FaDu, UTSCC8 and UTSCC42a) in addition to gene expression microarrays to identify over-expressed transcripts in the HNSCC cells in comparison to a normal control cell line. This integrated data set was systematically mined using publicly available resources (Human Protein Atlas and published proteomic/transcriptomic data) to prioritize putative candidates for validation. Subsequently, quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and ELISAs were performed to verify selected markers. Our integrated analyses identified 90 putative protein biomarkers that were secreted or shed to the extracellular space and over-expressed in HNSCC cell lines, relative to controls. Subsequently, the over-expression of five markers was verified in vitro at the transcriptional and translational levels using qRT-PCR and Western blotting, respectively. IHC-based validation conducted in two independent Head and Neck Squamous Cell Carcinoma (HNSCC)1 is the sixth most common cancer worldwide, with ϳ600,000 new cases diagnosed every year (1). HNSCCs include squamous cell carcinomas (SCCs) of the oral cavity, pharynx (nasopharynx, oropharynx, and hypopharynx), and larynx. Despite improvements in therapeutic approaches, the overall 5-year survival rate of HNSCC patients has not improved over the past three decades (1, 2).Clinical management of HNSCC is faced by several challenges, including early detection of the primary tumor, and site-specific control of the disease (3, 4). Early diagnosis is often hampered by the asymptomatic nature of HNSCC development and the inadequacy of current diagnostic methods to identify HNSCCs with sufficient specificity and sensitivity. As a result, over 60% of HNSCC patients present with advanced stages III or IV, harboring lymph node metastases (3).

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“…Because of their cellular homogeneity and ease of use, many studies have utilized human ovarian cancer lines for proteomics discovery. Such studies include comparisons of proteomic profiles between low-and high-grade serous epithelial cell lines (34); comparisons of lysate, membrane-associated, and secreted proteins between immortalized cell lines and primary ascites (21); global comparisons of secretomes across different epithelial ovarian cancer subtypes (20); and the identification of biomarkers associated with chemotherapeutic resistance in ovarian cancers (27).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

Marzinke

Choi

Chen

et al. 2013

Molecular & Cellular Proteomics

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While ovarian cancer remains the most lethal gynecological malignancy in the United States, there are no biomarkers available that are able to predict therapeutic responses to ovarian malignancies. One major hurdle in the identification of useful biomarkers has been the ability to obtain enough ovarian cancer cells from primary tissues diagnosed in the early stages of serous carcinomas, the most deadly subtype of ovarian tumor. In order to detect ovarian cancer in a state of hyperproliferation, we analyzed the implications of molecular signaling cascades in the ovarian cancer cell line OVCAR3 in a temporal manner, using a mass-spectrometry-based proteomics approach. OVCAR3 cells were treated with EGF 1 , and the time course of cell progression was monitored based on Akt phosphorylation and growth dynamics. EGF-stimulated Akt phosphorylation was detected at 12 h posttreatment, but an effect on proliferation was not observed until 48 h post-exposure. Growth-stimulated cellular lysates were analyzed for protein profiles between treatment groups and across time points using iTRAQ labeling and mass spectrometry. The protein response to EGF treatment was identified via iTRAQ analysis in EGF-stimulated lysates relative to vehicle-treated specimens across the treatment time course. Validation studies were performed on one of the differentially regulated proteins, lysosomal-associated membrane protein 1 (LAMP-1), in human tissue lysates and ovarian tumor tissue sections. Further, tissue microarray analysis was performed to demarcate LAMP-1 expression across different stages of epithelial ovarian cancers. These data support the use of this approach for the efficient identification of tissuebased markers in tumor development related to specific signaling pathways. LAMP-1 is a promising biomarker for studies of the progression of EGF-stimulated ovarian cancers and might be useful in predicting treatment responses involving tyrosine kinase inhibitors or EGF receptor monoclonal antibodies. Molecular & Cellular

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Comprehensive Analysis of Conditioned Media from Ovarian Cancer Cell Lines Identifies Novel Candidate Markers of Epithelial Ovarian Cancer

Cited by 73 publications

References 42 publications

Comparative secretome of ovarian serous carcinoma: Gelsolin in the spotlight

Comparative secretome of ovarian serous carcinoma: Gelsolin in the spotlight

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

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