The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Huong, Phung Thanh; Nguyen, Lap Thi; Nguyen, Xuan-Bac; Lee, Sang Kook; Bach, Duc-Hiep

doi:10.3390/cancers11020240

Cited by 111 publications

(101 citation statements)

References 127 publications

(137 reference statements)

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“…Indeed, PLTs may serve as circulating carriers of pro-tumor factors, thus acting systemically and locally in a beneficial manner regarding tumor progression and stimulating tumors to be resistant to therapies [23]. For this reason, unraveling the functional contribution of PLTs in tumor angiogenesis and growth may potentially provide better strategies for cancer treatment [24]. In this work, we hypothesized that the highly intense hypervascularization of GBM contributes to an overexposure of VWF on the GEC surface, thereby determining the massive recruitment and activation of circulating PLTs.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology

Campanella

Guarnaccia

Cordiglieri

et al. 2020

Cells

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Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors.Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of "tumor education", characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, Cells 2020, 9, 294 2 of 15 S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network's complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers.

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Section: Discussionmentioning

confidence: 99%

Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology

Campanella

Guarnaccia

Cordiglieri

et al. 2020

Cells

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“…Resistance to anticancer drugs is a complex process (5,(95)(96)(97)(98)(99)(100)(101)(102), and CIN-related phenotypic and genetic diversity in tumors has implications for chemotherapy-resistance including innate and acquired resistance (89). CIN-positive tumors seem to be more sensitive to DNA-damaging agents or radiotherapy (6) stability by using inhibitors of the microtubule-destabilizing kinase, Aurora B (104), may enhance chromosome missegregation; Aurora B inhibitors have shown efficacy in primary as well as taxane-resistant tumors (105,106).…”

Section: Combination With Chemotherapy To Overcome Resistancementioning

confidence: 99%

Chromosomal Instability in Tumor Initiation and Development

2019

Self Cite

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Chromosomal instability (CIN) is one of the major forms of genomic instability in various human cancers and is recognized as a common hallmark of tumorigenesis and heterogeneity. However, some malignant tumors show a paucity of chromosomal alterations, suggesting that tumor progression and evolution can occur in the absence of CIN. It is unclear whether CIN is stable between precursor lesions, primary tumor, and metastases or if it evolves during these steps. In this review, we describe the influence of CIN on the various steps in tumor initiation and development. Given the recognized significant effects of CIN in cancer, CIN-targeted therapeutics could have a major impact on improving clinical outcomes.

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“…[25][26][27] Furthermore, PPEF1 is involved in a variety of molecular functions related to tumor microenvironment, such as proteases, 28 platelet-derived growth factors and collagen. 29,30 Third, we have innovatively predicted the potential signaling pathways underlying the oncogenic activity of PPEF1 in BC by GSEA. The high expression of PPEF1 is mainly enriched in EMT, angiogenesis, TGF-β pathway, Focal adhesion and ECM receptor interaction (Figure 4, Table 3).…”

Section: Dovepressmentioning

confidence: 99%

<p>The Clinical Significance of <em>PPEF1</em> as a Promising Biomarker and Its Potential Mechanism in Breast Cancer</p>

Ye¹,

Wan²,

Li³

et al. 2020

OTT

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Background: Breast cancer (BC) is the leading cause of malignancy death in females worldwide. While intense efforts have been made to elucidate the pathogeny, the molecular mechanism of BC remains elusive. Thus, this study aimed to investigate the role of PPEF1 in the progression of BC and further explore the better clinical significance. Methods: The diagnostic and prognostic values of elevated PPEF1 expression in BC were unveiled via public databases analysis. In addition, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and Protein-protein interaction (PPI) analysis were performed to explore the potential functions and molecular mechanisms of PPEF1 in BC progression. Experimentally, transwell and CCK-8 assays were carried out to estimate the effects of PPEF1 on the BC metastasis. Meanwhile, the differential expressions of PPEF1 in paraffin-embedded tissues and serum samples were, respectively, analyzed by Immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) kit. Results: The transcriptional levels of PPEF1 were higher in BC than in normal breast tissues or adjacent normal tissues. Moreover, survival analysis revealed that higher PPEF1 expression was negatively associated with overall survival (OS), all events-free (AE-free) and metastatic recurrence-free (MR-free) survival, and further was an independent risk factor of unfavorable prognosis in BC patients. Additionally, the present study provided the first evidence that PPEF1 participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Furthermore, PPEF1 promotes the BC progression and can be used as a noninvasive diagnostic marker. Noteworthy, the combined determination of serum PPEF1 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of BC. Conclusion: PPEF1 exerted a tumorigenic role and involved in molecular mechanism of tumorigenesis in BC which served as a promising biomarker for prognosis and diagnosis.

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The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Cited by 111 publications

References 127 publications

Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology

Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology

Chromosomal Instability in Tumor Initiation and Development

<p>The Clinical Significance of <em>PPEF1</em> as a Promising Biomarker and Its Potential Mechanism in Breast Cancer</p>

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