Antiplatelet Agents Affecting GPCR Signaling Implicated in Tumor Metastasis

Rovati, G. Enrico; Contursi, Annalisa; Bruno, Annalisa; Tacconelli, Stefania; Ballerini, Patrizia; Patrignani, Paola

doi:10.3390/cells11040725

Cited by 7 publications

(5 citation statements)

References 192 publications

(254 reference statements)

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“…As expected, the thrombus blots treated with fibrin-targeting DiR/TGL NPs (FT-DT NPs) almost completely disappeared in an FeCl 3 -induced arterial thrombosis rat model (Figure B) . Moreover, taking into account of the crosstalk between platelets and tumor, P2Y12 receptor antagonist ticagrelor was also used to prominently suppress platelet-promoted tumor progression. − …”

Section: Platelet Modulation-based Nanotherapeuticsmentioning

confidence: 55%

Platelet-Inspired Nanotherapeutics for Biomedical Applications

Yang

Kong

et al. 2023

ACS Materials Lett.

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Platelets, as abundant corpuscles in the blood, are extensively involved in normal physiological processes and disease occurrence. Recently, remarkable progress in plateletbased nanotherapeutics has been made, especially with the burgeoning fields of biotechnology and nanomedicine. Herein, we aim to provide an overview on platelet-inspired nanotherapeutics for biomedical applications. First, the recent trends of biomimetic platelet-inspired nanotherapeutics are outlined, mainly including platelet membrane-camouflaged nanosystems, platelets loading with nanoparticles and platelet-mimicking nanocarriers. Then, the emerging nanotherapeutics for functional modulation of platelet aggregation, activation, and inhibition are discussed. Subsequently, platelet derivative-based nanotherapeutics are presented, including platelet extracellular vesicles and platelet polyphosphates. Finally, the clinical application prospects of these emerging nanotherapeutics are highlighted, with particular emphasis on their rationale, advantages, and challenges.

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Section: Platelet Modulation-based Nanotherapeuticsmentioning

confidence: 55%

Platelet-Inspired Nanotherapeutics for Biomedical Applications

Yang

Kong

et al. 2023

ACS Materials Lett.

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“…Platelets can also serve as a protective “cloak” to shield circulating tumor cells from immune destruction, playing a key role in tumor cell survival and metastasis. 35 Lymphocytes can induce cytotoxic cell death and cytokine secretion, inhibit tumor cell proliferation and migration, and control tumor growth. Additionally, lower lymphocyte counts are associated with a lower survival rate in cancer patients, likely due to the weakening of the host’s anticancer immunity as lymphocyte levels decrease.…”

Section: Discussionmentioning

confidence: 99%

CXCL9 Overexpression Predicts Better HCC Response to Anti-PD-1 Therapy and Promotes N1 Polarization of Neutrophils

Wang,

Xu,

et al. 2024

JHC

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Background Anti-programmed death-1 (PD1) antibodies have changed the treatment landscape for hepatocellular carcinoma (HCC) and exhibit promising treatment efficacy. However, the majority of HCCs still do not respond to anti-PD-1 therapy. Methods We analyzed the expression of CXCL9 in blood samples from patients who received anti-PD-1 therapy and evaluated its correlation with clinicopathological characteristics and treatment outcomes. Based on the results of Cox regression analysis, a nomogram was established for predicting HCC response to anti-PD-1 therapy. qRT‒PCR and multiple immunofluorescence assays were utilized to analyze the proportions of N1-type neutrophils in vitro and in tumor samples, respectively. Results The nomogram showed good predictive efficacy in the training and validation cohorts and may be useful for guiding clinical treatment of HCC patients. We also found that HCC cell-derived CXCL9 promoted N1 polarization of neutrophils in vitro and that AMG487, a specific CXCR3 inhibitor, significantly blocked this process. Moreover, multiple immunofluorescence (mIF) showed that patients with higher serum CXCL9 levels had greater infiltration of the N1 phenotype of tumor-associated neutrophils (TANs). Conclusion Our study highlights the critical role of CXCL9 as an effective biomarker of immunotherapy efficacy and in promoting the polarization of N1-type neutrophils; thus, targeting the CXCL9-CXCR3 axis could represent a novel pharmaceutical strategy to enhance immunotherapy for HCC.

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“…Aspirin, initially given to decrease platelet formation and risk of reinfarction in patients with myocardial infarction, significantly decreases cancer risk ( 96 ). Other anti-platelet therapy that interferes with production and release of AA may exert negative downstream effects on cancer cells ( 97 , 98 ). Examples of these include the P2Y12 inhibitor tricagrelor that inhibits tumor-platelet interaction and metastasis formation ( 99 ), as well as clopidogrel ( 100 ) and flavonoids with anti-COX and anti-cancer effects ( 101 , 102 ).…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus infection enhances 5‑lipoxygenase and cycloxygenase‑2 expression in colorectal cancer

Pantalone,

Almazan,

Lattanzio

et al. 2023

Int J Oncol

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Colorectal cancer (CRC) is one of the most common and fatal types of cancer. Inflammation promotes CRC development, however, the underlying etiological factors are unknown. Human cytomegalovirus (HCMV), a virus that induces inflammation and other cancer hallmarks, has been detected in several types of malignancy, including CRC. The present study investigated whether HCMV infection was associated with expression of the pro-inflammatory enzymes 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2) and other molecular, genetic and clinicopathological CRC features. The present study assessed 146 individual paraffin-embedded CRC tissue microarray (TMA) cores already characterized for TP53 and KRAS mutations, microsatellite instability (MSI) status, Ki-67 index and EGFR by immunohistochemistry (IHC). The cores were further analyzed by IHC for the expression of two HCMV proteins (Immediate Early, IE and pp65) and the inflammatory markers 5-LO and COX-2. The CRC cell lines Caco-2 and LS-174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or anti-inflammatory drug celecoxib (CCX) and analyzed by reverse transcription-quantitative PCR and immunofluorescence for 5-LO, COX-2, IE and pp65 transcripts and proteins. HCMV IE and pp65 proteins were detected in ~90% of the CRC cases tested; this was correlated with COX-2, 5-LO and KI-67 expression, but not with EGFR immunostaining, TP53 and KRAS mutations or MSI status. In vitro , HCMV infection upregulated 5-LO and COX-2 transcript and proteins in both Caco-2 and LS-174T cells and enhanced cell proliferation as determined by MTT assay. Treatment with GCV and CCX significantly decreased the transcript levels of COX-2, 5-LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy.

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Antiplatelet Agents Affecting GPCR Signaling Implicated in Tumor Metastasis

Cited by 7 publications

References 192 publications

Platelet-Inspired Nanotherapeutics for Biomedical Applications

Platelet-Inspired Nanotherapeutics for Biomedical Applications

CXCL9 Overexpression Predicts Better HCC Response to Anti-PD-1 Therapy and Promotes N1 Polarization of Neutrophils

Human cytomegalovirus infection enhances 5‑lipoxygenase and cycloxygenase‑2 expression in colorectal cancer

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