Prion proteins (PRNP and PRND) are over‐expressed in osteosarcoma

Sollazzo, Vincenzo; Galasso, Marco; Volinia, Stefano

doi:10.1002/jor.22034

Cited by 15 publications

(13 citation statements)

References 23 publications

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“…PRNP has been recently demonstrated to be involved in resistance to apoptosis, tumorigenesis, proliferation, and metastasis and its increased expression associated with other oncogenes seems to be involved in osteosarcoma development .…”

Section: Discussionsupporting

confidence: 78%

“…Although paucity of low-abundance peptides in serum makes their detection difficult without the use of nanoparticles technology, they can be considered markers of pathway activity providing information on impaired processes that drive tumor cells to malignant progression. PRNP has been recently demonstrated to be involved in resistance to apoptosis, tumorigenesis, proliferation, and metastasis and its increased expression associated with other oncogenes seems to be involved in osteosarcoma development [36].…”

Section: Discussionmentioning

confidence: 99%

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Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression

et al. 2016

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Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors for which identification and validation of biological markers may improve clinical management. The fraction of low-molecular-weight (LMW) circulating proteins and fragments of proteins is a rich source of new potential biomarkers. To identify circulating biomarkers useful for STS early diagnosis and prognosis, we analyzed 53 high-grade STS sera using hydrogel core-shell nanoparticles that selectively entrap LMW proteins by size exclusion and affinity chromatography, protect them from degradation and amplify their concentration for mass spectrometry detection. Twenty-two analytes mostly involved in inflammatory and immunological response, showed a progressive increase from benign to malignant STS with a relative difference in abundance, more than 50% when compared to healthy control. 16 of these were higher in metastatic compared to non-metastatic tumors. Cox's regression analysis revealed a statistical significant association between the abundance of lactotransferrin (LTF) and complement factor H-related 5 (CFHR5) and risk of metastasis. In particular, CFHR5 was associated with the risk of metastasis. The role of circulating proteins involved in metastatic progression will be crucial for a better understanding of STS biology and patient management.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression

et al. 2016

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“…The potential diagnostic or prognostic values of PrP expression in cancer have also been explored by several studies. It has been shown that PrP expression was up-regulated in various types of cancers, including GC, osteosarcoma, breast cancer, melanoma, pancreatic cancer and colon cancer 8 , 10 - 14 . PrP overexpression in cancerous tissues was generally associated with poor survival or response to chemotherapy 13 , 15 - 17 .…”

Section: Introductionmentioning

confidence: 99%

The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis

Tang¹,

Ma²,

Zhang³

et al. 2016

J. Cancer

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Previous reports indicated that prion protein (PrP) is involved in gastric cancer (GC) development and progression, but its role in GC prognosis has been poorly characterized. A total of 480 GC patients were recruited in this retrospective study. PrP expression in cancerous and non-cancerous gastric tissues was detected by using the tissue microarray and immunohistochemical staining techniques. Our results showed that the PrP expression in GC was significantly less frequent than that in the non-cancerous gastric tissue (44.4% vs 66.4%, P < 0.001). Cox regression analysis revealed that PrP expression was associated with TNM stage, survival status and survival time. GC patients with higher TNM stages (stages II, III and IV) had significantly lower PrP expression levels in tumors than those with lower TNM stages (stages 0 and I). Kaplan-Meier survival curves revealed that negative PrP expression was associated with poor overall survival (log-rank test: P < 0.001). The mean survival time for patients with negative PrP expression was significant lower than those with positive PrP expression (43.0±28.5m vs. 53.9±31.1m, P<0.001). In multivariate Cox hazard regression, PrP expression was an independent prognostic factor for GC survival, with a HR (hazard ratio) of 0.687 (95%CI:0.520-0.907, P=0.008). Our results revealed that negative PrP expression could independently predict worse outcome in GC and thereby could be used to guide the clinical practice.

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“…Several groups have reported that PrP expression is up-regulated in a variety of human cancers, including gastric carcinoma [8], [9], osteosarcoma [10], breast cancer [11], melanoma [12], and pancreatic cancer [13]. More importantly, at least two studies revealed that PrP expression is associated with poor prognosis in pancreatic and breast cancers [11], [13], suggesting a contributory role of PrP in cancer biology.…”

Section: Introductionmentioning

confidence: 99%

Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli

Jiang

et al. 2012

PLoS ONE

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Prion protein (PrP) is well studied for its pathogenic role in prion disease, but its potential contribution to other pathological processes is less understood. PrP is expressed in a variety of cancers and at least in pancreatic and breast cancers, its expression appears to be associated with poor prognosis. To understand the role of PrP in breast cancer cells, we knocked down PrP expression in MDA-MB-435 breast cancer cells with small interfering RNA and subjected these cells to a series of analyses. We found that PrP knockdown in these cells does not affect cell proliferation or colony formation, but significantly influences the cellular response to cytotoxic stimuli. Compared to control cells, PrP knockdown cells exhibited an increased susceptibility to serum deprivation induced apoptosis, no change to staurosporine- or paclitaxel-induced cell deaths, and a reduced susceptibility to chemotherapy drug doxorubicin-induced cell death. To understand the mechanism of unexpected role of PrP in exacerbating doxorubicin-induced cytotoxicity, we analyzed cell death related Bcl-2 family proteins. We found that PrP knockdown alters the expression of several Bcl-2 family proteins, correlating with increased resistance to doxorubicin-induced cytotoxicity. Moreover, the enhanced doxorubicin resistance is independent of DNA damage related p53 pathway, but at least partially through the ERK1/2 pathway. Together, our study revealed that silencing PrP in MDA-MB-435 breast cancer cells results in very different responses to various cytotoxic stimuli and ERK1/2 signaling pathway is involved in PrP silencing caused resistance to doxorubicin.

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Prion proteins (PRNP and PRND) are over‐expressed in osteosarcoma

Cited by 15 publications

References 23 publications

Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression

Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression

The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis

Silencing Prion Protein in MDA-MB-435 Breast Cancer Cells Leads to Pleiotropic Cellular Responses to Cytotoxic Stimuli

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