An integrated cell line-based discovery strategy identified follistatin and kallikrein 6 as serum biomarker candidates of breast carcinoma

Mangé, Alain; Dimitrakopoulos, Lampros; Soosaipillai, Antoninus; Coopman, Peter J.; Diamandis, Eleftherios P.; Solassol, Jérôme

doi:10.1016/j.jprot.2016.04.050

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…Over the past decade, KLK6 has emerged as a significant player in various stages of cancer development, and it has been associated with cell malignancy in multiple cancers, including melanoma, ovarian, colon, gastric and breast cancers (8,19,21,23). Previous studies from the Mori laboratory demonstrated that siRNA silencing of KLK6 expression in gastric cancer cells can inhibit a variety of malignant phenotypes, implicating KLK6 as a therapeutic target in cancer (14).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, in colon cancer, in which KLK6 can be used for both prognosis and diagnosis, it induces the invasiveness and proliferation of cancer cells by down-regulating E-cadherin, thereby interrupting E-cadherin-mediated cell-cell adhesion -a prerequisite for tumor invasiveness and metastasis (14,16,21). Moreover, KLK6 appears to be relevant for breast cancer, as high KLK6 expression levels were recently shown to promote the invasiveness of breast cancer cells; KLK6 serum levels were found to be significantly higher in patients with invasive breast cancer, and patients with high KLK6 expression showed poorer survival rates (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

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A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering

Sananes

Cohen

Shahar

et al. 2018

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering

Sananes

Cohen

Shahar

et al. 2018

Journal of Biological Chemistry

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“…The media was supplemented with 5% Horse Serum (Life Technologies Corporation, Carlsbad, CA), 10ug/mL bovine insulin (Cell applications Inc, San Diego, CA), 500ng/mL hydrocortisone (BioXtra, Sigma Aldrich, St. Louis), 20ng/mL epithelial growth factor (Millipore Sigma, Temecula, CA). The CA1D is a transformed human breast epithelial cell line from pre-malignant tissue (34,35). The pancreatic cell lines HPV16 E6/E7 cells and PANC1 cells were cultured in regular cell media mixture of DMEM (Gibco, Life Technologies, Carlsbad, CA) + 10% FBS (Gibco, Life Technologies, Carlsbad, CA) + 1% penicillin-streptomycin (Gibco, Life Technologies, Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

Autofluorescence lifetime imaging of cellular metabolism: Sensitivity toward cell density, pH, intracellular, and intercellular heterogeneity

Chacko

Eliceiri

2018

Cytometry Pt A

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Autofluorescence imaging (AFI) has greatly accelerated in the last decade, way past its origins in detecting endogenous signals in biological tissues to identify differences between samples. There are many endogenous fluorescence sources of contrast but the most robust and widely utilized have been those associated with metabolism. The intrinsically fluorescent metabolic cofactors Nicotinamide adenine dinucleotide (NAD+/NADH) and Flavin adenine dinucleotide (FAD/FADH2) have been utilized in a number of AFI applications including basic research, clinical and pharmaceutical studies. Fluorescence lifetime imaging microscopy (FLIM) has emerged as one of the more powerful AFI tools for NADH and FAD characterization due to its unique ability to non-invasively detect metabolite bound and free states and quantitate cellular redox ratio. However, despite this widespread biological use, many standardization methods are still needed to extend FLIM based AFI into a fully robust research and clinical diagnostic tools. FLIM is sensitive to a wide range of factors in the fluorophore microenvironment and there a number of analysis variables as well. To this end there has been an emphasis on developing imaging standards and ways to make the image acquisition and analysis more consistent. However biological conditions during FLIM based AFI imaging are rarely considered as key sources of FLIM variability. Here we present several experimental factors with supporting data of the cellular microenvironment such as confluency, pH, inter/intra cellular heterogeneity, and choice of cell line that need to be considered for accurate quantitative FLIM based AFI measurement of cellular metabolism.

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“…FST binds activin to inhibit its activity 34) , and dysregulation of the FST and activin axis is one of the most significant factors underlying tumor genesis. FST has been reported as a biomarker or therapeutic target in cancers such as breast cancer 35) , ovarian cancer 36,37) , hepatocellular carcinoma 23) , and glioblastoma 38) . Recently, Chen et al reported that FST is a novel biomarker for the diagnosis of lung adenocarcinoma 22) .…”

Section: Discussionmentioning

confidence: 99%

Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

Qiao

Kito²,

Takai³

et al. 2017

J. Electrophor

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SUMMARYSarcoma is a rare malignancy with an aggressive clinical course. Tyrosine kinase inhibitors (TKIs) have emerged as effective drugs in targeted therapy for malignancies; in particular, pazopanib was recently approved for the treatment of sarcoma. However, as only a limited proportion of patients exhibit favorable response to treatment with TKIs, predictive biomarkers of response to these drugs are urgently needed. In this study, we attempted to identify predictive biomarkers for response to TKIs in synovial sarcoma. We performed a magnetic bead-based assay (Bio-Plex) using synovial sarcoma cell culture supernatant and validated the results by ELISA and western blotting. Cellular protein and mRNA expression levels of candidate biomarkers were evaluated by western blotting and RT-PCR. Gene expression profiling of candidate biomarkers was conducted by meta-analysis of publicly available gene expression data from 149 patients with synovial sarcoma. We found that follistatin (FST) was significantly highly expressed in TKI-resistant cells. Moreover, cell proliferation was decreased following gene silencing of FST. Meta-analysis revealed that the mRNA expression of FST varied among the 149 patients with synovial sarcoma, and that 23 genes were co-expressed with FST; these included genes encoding receptor tyrosine kinase-like orphan receptor 1, Sal-like protein 4, and signal transducer CD24. This study suggested that FST represents a candidate predictive biomarker for response to treatment with TKIs in synovial sarcoma. Secretomics is a promising approach for predictive biomarker exploration. The utility of FST as a predictive biomarker for response to treatment with TKIs in synovial sarcoma should be further validated using clinical samples.

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An integrated cell line-based discovery strategy identified follistatin and kallikrein 6 as serum biomarker candidates of breast carcinoma

Cited by 23 publications

References 41 publications

A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering

A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering

Autofluorescence lifetime imaging of cellular metabolism: Sensitivity toward cell density, pH, intracellular, and intercellular heterogeneity

Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

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