Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis

Losi, Lorena; Parenti, Sandra; Ferrarini, Fabrizio; Rivasi, Francesco; Gavioli, M.; Natalini, Gianni; Ferrari, Sérgio; Grande, Alexis

doi:10.1016/j.humpath.2010.10.009

Cited by 20 publications

(33 citation statements)

References 30 publications

(33 reference statements)

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“…These findings confirmed the data that have been previously published by our and other research groups, indicating a controversial role of E-cadherin in CRC [4,[18][19][20] The expression changes detected for some of the other cadherin superfamily members, exhibiting a down-regulated (PCDH24) or upregulated (CDH3) expression in the tumor progression process from normal colorectal mucosa to colorectal adenoma and carcinoma, have been already observed by other authors [21,22], demonstrating the reliability of our bioinformatic analysis conditions. Based on previous reports evidencing that the lack of expression of cadherin genes is rarely due to gene mutations [23] and it is more frequently the consequence of epigenetic changes [24,25] we perfomed a methylation analysis of μ-protocadherin promoter region in colorectal adenomas/carcinomas and CRC cell lines.…”

Section: Discussionsupporting

confidence: 91%

“…Recently, data obtained in our laboratory have allowed us to demonstrate the involvement of a cadherin superfamily protein, named μ-protocadherin, in CRC, where we observed a complete loss of its expression in the majority of analyzed cases [4].…”

Section: Discussionmentioning

confidence: 71%

“…In fact, in CRC cases, this DNA region exhibited a methylation pattern that was substantially superimposable to that observed in the CpG2 island whereas in CRC cell lines it appeared unmethylated in CaCo2 and HT29 cells, characterized by a detectable μ-protocadherin expression (although exclusively with RT-PCR) and a less transformed tumor phenotype, and strongly methylated in HCT116 and LoVo cells, carrying the opposite features [4] (Figure 6). …”

Section: Methylation Analysis Of Mupcdh Promoter Region In Colorectalmentioning

confidence: 92%

“…Immunoperoxidase staining was run with the Benchmark XT Automatic Staining System (Ventana, Strasbourg, France) using a rabbit policlonal anti-human μ-protocadherin antibody (MUPCDH) (Sigma, St. Louis, USA) at dilution 1:100. The presence of immunoreactive neoplastic cells stained for μ-protocadherin was graded as previously described [4].…”

Section: Immunohistochemical Analysis Of Colorectal Adenomas and Carcmentioning

confidence: 99%

“…In fact, the E-cadherin/β-catenin complex has the capacity to suppress either the proliferation or the invasion of epithelial cells in normal conditions [1] and downregulation of E-cadherin expression facilitates the acquisition of these properties by cancer cells [2] Several reports, published over the last decade, have highlighted the existence of a novel cadherin family member that has been called μ-protocadherin, to underline the hybrid nature of its extra-cellular region, characterized by the presence of both cadherin-and mucinlike domains [3]. Unlike other protocadherins, exhibiting a preferential expression in the nervous system, this protein is detectable in a number of different tissues including colorectal mucosa, where it is down-regulated during CRC tumor progression [4] and up-regulated upon treatment with chemoprevention agents against this neoplastic condition [5]. These findings suggested that μ-protocadherin determines an onco-suppressive effect on normal colon enterocytes, also supported by the observation that, as other cadherins, it is able to sequester and inhibit β-catenin [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

Benhattar¹

2014

J Carcinog Mutagen

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Mu-protocadherin is a membrane protein belonging to the cadherin superfamily that, as the other members, promotes inter-cellular adhesion and proliferation arrest. Notably, both these onco-suppressive activities are mediated by its capacity to inhibit the β-catenin signaling pathway, that is constitutively activated in colorectal cancer (CRC) and, not surprisingly, its expression undergoes a remarkable down-regulation in CRC, although this finding has been to date only achieved in a limited set of patients. Based on this premise, the aims of our study were: (1) to confirm the down-regulated expression of μ-protocadherin in a larger cohort of CRC patients; (2) to assess the possible relationship existing between the expression levels of this protein and the clinical-pathological parameters of the disease; (3) to identify the molecular mechanism underlying the decrease of its expression occuring in CRC.To address these issues, we developed a database containing more than one thousand CRC expression profiles, recovered by GEO (Gene Expression Omnibus) and supplied with a significant set of clinical information, that was subsequently used to perform a bioinformatic analysis of cadherin genes. A methylation analysis of μ-protocadherin gene promoter was also carried out, using the bisulfite pyro-sequencing procedure, in an independent series of CRC samples. The results obtained confirmed the down-regulation of μ-protocadherin expression in CRC, suggested a possible prognostic role for this alteration and indicated the promoter hyper-methylation of its gene as the responsible mechanism.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 71%

Section: Methylation Analysis Of Mupcdh Promoter Region In Colorectalmentioning

confidence: 92%

Section: Immunohistochemical Analysis Of Colorectal Adenomas and Carcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

Benhattar¹

2014

J Carcinog Mutagen

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Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

Piccoli

D’Angelo

Crotti

et al. 2018

Journal Cellular Physiology

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Three-dimensional (3D) cancer models are overlooking the scientific landscape with the primary goal of bridging the gaps between two-dimensional (2D) cell lines, animal models and clinical research. Here, we describe an innovative tissue engineering approach applied to colorectal cancer (CRC) starting from decellularized human biopsies in order to generate an organotypic 3D-bioactive model. This in vitro 3D system recapitulates the ultrastructural environment of native tissue as demonstrated by histology, immunohistochemistry, immunofluorescence and scanning electron microscopy analyses. Mass spectrometry of proteome and secretome confirmed a different stromal composition between decellularized healthy mucosa and CRC in terms of structural and secreted proteins. Importantly, we proved that our 3D acellular matrices retained their biological properties: using CAM assay, we observed a decreased angiogenic potential in decellularized CRC compared with healthy tissue, caused by direct effect of DEFA3. We demonstrated that following a 5 days of recellularization with HT-29 cell line, the 3D tumor matrices induced an over-expression of IL-8, a DEFA3-mediated pathway and a mandatory chemokine in cancer growth and proliferation. Given the biological activity maintained by the scaffolds after decellularization, we believe this approach is a powerful tool for future pre-clinical research and screenings.

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CDHR5 inhibits proliferation of hepatocellular carcinoma and predicts clinical prognosis

et al. 2019

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Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis

Cited by 20 publications

References 30 publications

Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

CDHR5 inhibits proliferation of hepatocellular carcinoma and predicts clinical prognosis

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