PDGFRα/β expression correlates with the metastatic behavior of human colorectal cancer: A possible rationale for a molecular targeting strategy

Wehler, Thomas; Frerichs, Kirsten; Graf, Claudine; Drescher, Daniel; Schimanski, Katrin; Biesterfeld, Stefan; Berger, Martin R.; Kanzler, Stephan; Junginger, Theodor; Galle, Peter R.; Moehler, Markus; Gockel, Ines; Schimanski, Carl Christoph

doi:10.3892/or.19.3.697

Cited by 32 publications

(39 citation statements)

References 29 publications

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“…The overexpression of PDGFRs in CRC is related to angiogenesis, invasion, and metastasis as well as poor survival and target associated therapy (Table 1). In a previous study Wehler et al [46] reported that the majority of CRC specimens investigated in 99 cohort patients revealed a PDGFR- α / β expression and this expression was significantly correlated with lymphatic dissemination and metastatic disease. Furthermore, Steller et al [44] found that high PDGFR- β expression in CRC tumors could be associated with the occurrence of metastasis.…”

Section: The Role Of Pdgfrs In Colorectal Carcinogenesismentioning

confidence: 99%

The Role of PDGFs and PDGFRs in Colorectal Cancer

Saplacan

Bălăcescu

Gherman

et al. 2017

Mediators of Inflammation

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Introduction. Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Angiogenesis was reported as one important mechanism activated in colorectal carcinogenesis. Tumor microenvironment associated angiogenesis involves a large spectrum of signaling molecules and deciphering their role in colorectal carcinogenesis still represents a major challenge. The aim of our study is to point out the diagnosis and prediction role of PDGF family and their receptors in colorectal carcinogenesis. Material and Methods. A systematic search in Medline and PubMed for studies reporting the role of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in tumor biology related to CRC was made. Results. PDGFs are important growth factors for normal tissue growth and division, with an important role in blood vessel formation. PDGFs/PDGFRs signaling pathway has been demonstrated to be involved in angiogenesis mainly by targeting pericytes and vascular smooth muscle cells. High levels of PDGF-BB were reported in CRC patients compared to those with adenomas, while elevated levels of PDGFR α/β in the stroma of CRC patients were correlated with invasion and metastasis. Moreover, PDGF-AB and PDGF-C were correlated with early diagnosis, cancer grading, and metastatic disease. Conclusions. Both PDGFs and PDGFRs families play an important role in colorectal carcinogenesis and could be considered to be investigated as useful biomarkers both for diagnosis and treatment of CRC.

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Section: The Role Of Pdgfrs In Colorectal Carcinogenesismentioning

confidence: 99%

The Role of PDGFs and PDGFRs in Colorectal Cancer

Saplacan

Bălăcescu

Gherman

et al. 2017

Mediators of Inflammation

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“…Welher et al reported that PDGFRα was overexpressed in 83% of CRC specimens and significantly correlated with lymph node metastasis and advanced UICC stages III/IV in older patients [19]. Zhu et al revealed that the 3-year overall and progression-free survival rates were significantly lower in patients with high PDGFRα expression than in those with low PDGFRα expression [33].…”

Section: Discussionmentioning

confidence: 99%

“…Recent research revealed that PDGFR was upregulated in CRC and correlated with advanced tumor stage and lymph node metastasis [19]. Moreover, high PDGFRβ tumor stromal expression was mainly responsible for tumor metastasis [20], and PDGFRα co-expression with VEGFR significantly linked to Kras codon 12 or 13 mutations in CRC [21].…”

mentioning

confidence: 99%

MicroRNA-219-5p functions as a tumor suppressor partially by targeting platelet-derived growth factor receptor alpha in colorectal cancer

Gb¹,

Gn²,

Xiao³

et al. 2015

neo

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Platelet-derived growth factor receptor (PDGFR) signaling pathway was involved in the progress of colorectal cancer (CRC). By using the bioinformatic system online, we found that PDGFRα is a potential target of miR-219-5p. However, the expression pattern and underlying mechanisms of miR-219-5p had not been elucidated in CRC. Herein, we first evaluated the expression of miR-219-5p in tumor tissues by real-time polymerase chain reaction. Next, we confirmed that PDGFRα is the target of miR-219-5p by using luciferase report. And then, we investigated the biological functions of miR-219-5p in vitro in cell proliferation and apoptosis as well as cell cycle by gain and loss of function strategies. Data shown that miR-219-5p is down-regulated in CRC tissues compared with the corresponding matched normal tissues. PDGFRα was a direct target of miR-219-5p. Overexpression of miR-219-5p could inhibit cell proliferation, promote cell apoptosis and induce cell cycle arrest at the G1 phase. Furthermore, miR-219-5p suppressed the activation of the phosphatidylinositol 3-kinase/Akt signaling pathway and downregulated G1 cell-cycle-related protein cyclin D1, cyclin-dependent kinase (CDK) 4, and CDK6. Taken together, our results demonstrate that miR-219-5p functions as a tumor suppressor partially by targeting PDGFRα in colorectal cancer.

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“…The chemokine ligand 1 receptor, CCL1, has been implicated in cancer before and also it has been suggested as a therapeutic target in this context [45]. Platelet derived growth factor C (PDGFC) is part of the PDGFR-alpha signalling pathway and the influence of PDGFR expression on metastatic behaviour has been well documented [46]. STAT1 is involved in cell growth processes [47], hence its appearance in this list is reasonable.…”

Section: Biological Interpretation Of the Most Discriminative Proteinsmentioning

confidence: 99%

Predicting Genes Involved in Human Cancer Using Network Contextual Information

Rahmani

Blockeel

Bender

2012

Journal of Integrative Bioinformatics

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SummaryProtein-Protein Interaction (PPI) networks have been widely used for the task of predicting proteins involved in cancer. Previous research has shown that functional information about the protein for which a prediction is made, proximity to specific other proteins in the PPI network, as well as local network structure are informative features in this respect. In this work, we introduce two new types of input features, reflecting additional information: (1) Functional Context: the functions of proteins interacting with the target protein (rather than the protein itself); and (2) Structural Context: the relative position of the target protein with respect to specific other proteins selected according to a novel ANOVA (analysis of variance) based measure. We also introduce a selection strategy to pinpoint the most informative features. Results show that the proposed feature types and feature selection strategy yield informative features. A standard machine learning method (Naive Bayes) that uses the features proposed here outperforms the current state-of-the-art methods by more than 5% with respect to F-measure. In addition, manual inspection confirms the biological relevance of the top-ranked features.

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PDGFRα/β expression correlates with the metastatic behavior of human colorectal cancer: A possible rationale for a molecular targeting strategy

Cited by 32 publications

References 29 publications

The Role of PDGFs and PDGFRs in Colorectal Cancer

The Role of PDGFs and PDGFRs in Colorectal Cancer

MicroRNA-219-5p functions as a tumor suppressor partially by targeting platelet-derived growth factor receptor alpha in colorectal cancer

Predicting Genes Involved in Human Cancer Using Network Contextual Information

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