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The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer.

ABSTRACT: Cellular prion protein (PrP^C) is seminal to modulate a variety of baseline cell functions to grant homeostasis. The classic role of such a protein was defined as a chaperone-like molecule being able to rescue cell survival. Nonetheless, PrP^C also represents the precursor of the deleterious misfolded variant known as scrapie prion protein (PrP^Sc). This variant is detrimental in a variety of prion disorders. This multi-faceted role of PrP is greatly increased by recent findings showing how PrP^C in its folded conformation may foster tumor progression by acting at multiple levels. The present review focuses on such a cancer-promoting effect. The manuscript analyzes recent findings on the occurrence of PrP^C in various cancers and discusses the multiple effects, which sustain cancer progression. Within this frame, the effects of PrP^C on stemness and differentiation are discussed. A special emphasis is provided on the spreading of PrP^C and the epigenetic effects, which are induced in neighboring cells to activate cancer-related genes. These detrimental effects are further discussed in relation to the aberrancy of its physiological and beneficial role on cell homeostasis. A specific paragraph is dedicated to the role of PrP^C beyond its effects in the biology of cancer to represent a potential biomarker in the follow up of patients following surgical resection.

SUBMITTER: Ryskalin L

PROVIDER: S-EPMC7825291 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer.

Ryskalin Larisa L Biagioni Francesca F Busceti Carla L CL Giambelluca Maria A MA Morelli Luca L Frati Alessandro A Fornai Francesco F

Cancers 20210106 2

Cellular prion protein (PrPC) is seminal to modulate a variety of baseline cell functions to grant homeostasis. The classic role of such a protein was defined as a chaperone-like molecule being able to rescue cell survival. Nonetheless, PrPC also represents the precursor of the deleterious misfolded variant known as scrapie prion protein (PrPSc). This variant is detrimental in a variety of prion disorders. This multi-faceted role of PrP is greatly increased by re ...[more]

PMID: 33418999

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Project description:Background:Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (?-Syn) and cellular prion protein (PrPC) is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether ?-Syn or PrPC overexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA). Methods:EA cells were treated with conditioned media (CM) of LS 174T-?-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays. To investigate plausible background mechanisms in conferring the properties of EA cells above, nitrite oxide (NO) levels were measured and the expression of angiogenesis-related factors was assessed using a human angiogenesis antibody array. Results:EA proliferation was significantly inhibited by LS 174T-PrP CM whereas its telomerase activity was reduced by CM of LS 174T-?-Syn or LS 174T-PrP, as compared to EA incubated with LS 174T CM. Besides, LS 174T-?-Syn CM or LS 174T-PrP CM inhibited EA invasion and migration in Boyden chamber assay. Furthermore, LS 174T-?-Syn CM significantly inhibited EA migration in scratch wound assay. Gelatin zymography revealed reduced secretion of MMP-2 and MMP-9 by EA treated with LS 174T-?-Syn CM or LS 174T-PrP CM. In addition, cell adhesion assay showed lesser LS 174T-?-Syn or LS 174T-PrP cells adhered onto EA, as compared to LS 174T. In tube formation assay, LS 174T-?-Syn CM or LS 174T-PrP CM induced EA tube formation. Increased NO secretion by EA treated with LS 174T-?-Syn CM or LS 174T-PrP CM was also detected. Lastly, decreased expression of pro-angiogenic factors like CXCL16, IGFBP-2 and amphiregulin in LS 174T-?-Syn CM or LS 174T-PrP CM was detected using the angiogenesis antibody array. Discussion:These results suggest that overexpression of ?-Syn or PrPC could possibly be involved in colorectal cancer-induced angiogenesis by inducing an endothelial proliferation-differentiation switch. NO could be the main factor in governing this switch, and modulation on the secretion patterns of angiogenesis-related proteins could be the strategy of colorectal cancer cells overexpressing ?-Syn or PrPC in ensuring this transition.

Dataset Information

The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer.

Publications

The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer.

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