Candidate Serum Biomarkers for Prostate Adenocarcinoma Identified by mRNA Differences in Prostate Tissue and Verified with Protein Measurements in Tissue and Blood

Klee, Eric W.; Bondar, Olga P.; Goodmanson, Marcia K.; Dyer, Roy B.; Erdoğan, Sibel; Bergstralh, Eric J.; Bergen, H. Robert; Sebo, Thomas J.; Klee, George G.

doi:10.1373/clinchem.2011.171637

Cited by 54 publications

(52 citation statements)

References 29 publications

(30 reference statements)

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“…ASPN, a new member of the SLRPs, is expressed abundantly in several malignant tumors, suggesting its involvement in the tumorigenesis and progression of cancer (6). Our present results, consistent with previous studies, revealed a significantly elevated ASPN expression in carcinoma tissues relative to the matched adjacent non-tumor tissues (11)(12)(13)(14). In addition, ASPN had varied expression in an inverse trend according to the differentiation degree of gastric cancer epithelial cell lines, hinting its oncogenic property, to some extent.…”

Section: Discussionsupporting

confidence: 92%

“…Particularly, Satoyoshi et al recently concluded that ASPN activates the coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts by activation of the CD44-Rac1 pathway (7). In addition, by applying quantitative mass spectrometry, innovative proteomic technologies or microarray analysis, ASPN was proven to be upregulated in a series of cancers, including pancreatic cancer (11), pancreatic ductal adenocarcinoma (12), prostate cancer (13) and breast carcinoma (14). In osteoarthritis, Kizawa et al found a direct interaction between ASPN and TGF-β.…”

Section: Introductionmentioning

confidence: 99%

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Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

2015

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Abstract. Asporin (ASPN), a novel member of the small leucine-rich proteoglycan (SLRP) family, serves as a key component of the tumor stroma and has been reported to be abnormally expressed in certain types of tumors. Specifically, the proteoglycan was proven to activate the coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. However, the role of ASPN in cancer cell growth and metastasis has not yet been addressed. In the present study, we aimed to evaluate the tumoricidal benefits of ASPN on tumorigenesis and progression of gastric cancer. Firstly, it was demonstrated that ASPN was overexpressed in gastric carcinoma tissues when compared to the corresponding non-cancerous tissues, and it had varied levels of expression in gastric cancer epithelial cell lines. Additionally, we assessed the effects of transient siRNA-mediated ASPN knockdown on gastric cancer cells. ASPN silencing inhibited proliferation and suppressed the migration of immortalized neoplastic epithelial cells. Furthermore, at the molecular level, we found that downregulation of ASPN blocked the anti-apoptotic molecule Bcl-2, increased the expression of pro-apoptotic molecule Bad, reduced the expression of migration-related proteins CD44 and matrix metalloproteinase (MMP)-2, and abrogated the activation of the phosphorylation status of ERK and epidermal growth factor (EGF) and its receptor (EGFR). Collectively, our findings indicate that ASPN is upregulated and plays an oncogenic role in gastric cancer progression and metastasis by influencing the EGFR signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

2015

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“…The overexpression of PACE4 in prostate cancer has been documented; however, no correlations with clinical parameters, such as Gleason grading, have been reported (6,13,14). New molecular markers with relevance to prostate cancer progression should show a positive correlation with the established histologic prognostic indicator, that is, Gleason grading, to be considered of prognostic usefulness.…”

Section: Resultsmentioning

confidence: 99%

PACE4 Undergoes an Oncogenic Alternative Splicing Switch in Cancer

et al. 2017

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Inhibition of PACE4, a proprotein convertase that is overexpressed in prostate cancer, has been shown to block cancer progression in an androgen-independent manner. However, the basis for its overexpression and its growth-inhibitory effects are mitigated and uncertain. Here, we report that PACE4 pre-mRNA undergoes DNA methylation-sensitive alternative splicing of its terminal exon 3 0 untranslated region, generating an oncogenic, C-terminally modified isoform (PACE4-altCT). We found this isoform to be strongly expressed in prostate cancer cells, where it displayed an enhanced autoactivating process and a distinct intracellular routing that prevented its extracellular secretion. Together, these events led to a dramatic increase in processing of the progrowth differentiation factor pro-GDF15 as the first PACE4 substrate to be identified in prostate cancer. We detected robust expression of PACE4-altCT in other cancer types, suggesting that an oncogenic switch for this proenzyme may offer a therapeutic target not only in advanced prostate cancer but perhaps also more broadly in human cancer. Cancer Res; 77(24); 6863-79. Ó2017 AACR.

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“…19,27 Apart from PCSK9, which plays a critical part in the regulation of lipid homeostasis, 28 other PCs have been poorly characterized in cardiovascular diseases, especially in comparison with their well-documented functions in cancers. PCSK6 involvement in prostate cancer has been extensively studied, the protein itself proposed as a serum biomarker, 29 and even a selective PCSK6 inhibitor with antiproliferative effects on prostate cancer cells was recently developed. 30 It has been suggested that Furin and PCSK5 modulate inflammatory responses, 31 regulate membrane-type MMPs and integrin-processing in atherosclerosis, 32 whereas PCSK7 and PCSK2 have been detected in vascular SMCs and linked to myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Atherosclerotic Lesions by Gene and Tissue Microarrays Reveals PCSK6 as a Novel Protease in Unstable Carotid Atherosclerosis

Perisic

Hedin

Razuvaev

et al. 2013

ATVB

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Objective— Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways is still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in a biobank of carotid endarterectomies followed by characterization of identified candidates, as a platform for discovery of novel proteins differentially regulated in unstable carotid lesions. Approach and Results— Genes highly upregulated in symptomatic versus asymptomatic plaques were selected from Affymetrix microarray analyses (n=127 plaques), and tissue microarrays constructed from 34 lesions were assayed for 21 corresponding proteins by immunohistochemistry. Quantification of stainings demonstrated differential expression of CD36, CD137, and DOCK7 ( P <0.05) in unstable versus stable lesions and the most significant upregulation of a proprotein convertase, PCSK6 ( P <0.0001). Increased expression of PCSK6 in symptomatic lesions was verified by quantitative real-time polymerase chain reaction (n=233), and the protein was localized to smooth muscle α-actin positive cells and extracellular matrix of the fibrous cap by immunohistochemistry. PCSK6 expression positively correlated to genes associated with inflammation, matrix degradation, and mitogens in microarrays. Stimulation of human carotid smooth muscle cells in vitro with cytokines caused rapid induction of PCSK6 mRNA. Conclusions— Using a combination of transcriptomic and tissue microarray profiling, we demonstrate a novel approach to identify proteins differentially expressed in unstable carotid atherosclerosis. The proprotein convertase PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. Further studies are needed to clarify the role of PCSK6 in atherosclerosis.

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Candidate Serum Biomarkers for Prostate Adenocarcinoma Identified by mRNA Differences in Prostate Tissue and Verified with Protein Measurements in Tissue and Blood

Cited by 54 publications

References 29 publications

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

PACE4 Undergoes an Oncogenic Alternative Splicing Switch in Cancer

Profiling of Atherosclerotic Lesions by Gene and Tissue Microarrays Reveals PCSK6 as a Novel Protease in Unstable Carotid Atherosclerosis

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