Platelets as crucial partners for tumor metastasis: from mechanistic aspects to pharmacological targeting

Contursi, Annalisa; Sacco, Angela; Grande, Rosalia; Dovizio, Melania; Patrignani, Paola

doi:10.1007/s00018-017-2536-7

Cited by 66 publications

(54 citation statements)

References 142 publications

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“…6 In addition, platelets form aggregates surrounding cancer cells, hampering the action of the immune system and thus facilitating the invasiveness of cancer cells to other locations. 17,18 All these data together further substantiate that the chemoprotective effect of low-dose aspirin is mediated, at least in part, by its antiplatelet effect. 18 This hypothesis would be reinforced if other antiplatelet drugs acting through a mechanism unrelated to COX inhibition also were associated with a decreased risk of CRC.…”

Section: Discussionmentioning

confidence: 65%

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer

Rodríguez‐Miguel

Garcı́a-Rodrı́guez

Gil³

et al. 2019

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS:The antiplatelet effect of low-dose aspirin, via inhibition of cyclooxygenase-1, might contribute to its ability to reduce the risk of colorectal cancer (CRC). Antiplatelet agents with a different mechanism, such as clopidogrel, might have the same effects. We aimed to quantify the effects of low-dose aspirin and clopidogrel on the risk of CRC in a Mediterranean population. METHODS:We performed a nested case-control study using a primary care database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria) in Spain. We collected data, from 2001 through 2014, on 15,491 incident cases of CRC and 60,000 randomly selected individuals (controls), frequency-matched to cases by age, sex, and year. To estimate the association between exposure to different antiplatelet agents and the risk of colorectal cancer, we built multiple logistic regression models and computed the adjusted-odds ratios (AORs) and their respective 95% CIs. RESULTS:Use of low-dose aspirin was associated with a reduced risk of CRC overall (AOR, 0.83; 95% CI, 0.78-0.89) and in patients receiving treatment for more than 1 year (AOR, 0.79; 95% CI, 0.73-0.85). Use of clopidogrel was associated with a decreased risk of CRC overall (AOR, 0.8; 95% CI, 0.69-0.93) and in patients receiving treatment for more than 1 year (AOR, 0.65; 95% CI, 0.55-0.78). Dual antiplatelet therapy had the same effect as either drug taken as monotherapy. No modification by sex or age was observed. CONCLUSIONS:In a nested case-control study of a primary care database in Spain, we found clopidogrel use, alone or in combination with low-dose aspirin, to reduce the risk of CRC by 20% to 30%, a magnitude similar to that of low-dose aspirin alone. These data support the concept that inhibiting platelets is an effective strategy for prevention of CRC.

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Section: Discussionmentioning

confidence: 65%

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer

Rodríguez‐Miguel

Garcı́a-Rodrı́guez

Gil³

et al. 2019

Clinical Gastroenterology and Hepatology

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“…There is evidence which indicates that platelets facilitate tumorigenesis through the association between platelet activation and the development of chronic inflammation. 8 Clinical evidence has shown that thrombocytosis is associated with adverse prognosis in various types of cancer, including ovarian cancer, lung cancer, gastric cancer, inflammatory breast cancer and colorectal cancer. [9][10][11][12][13] Platelet distribution width (PDW), an index of platelet size heterogeneity-another platelet index distinguished from mean platelet volume (MPV)-indicates a difference in platelet size.…”

Section: Introductionmentioning

confidence: 99%

The preoperative platelet distribution width: A predictive factor of the prognosis in patients with non‐small cell lung cancer

Liu

Zhang

et al. 2020

Thoracic Cancer

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Background The prognostic value of platelet distribution width (PDW) is different in various malignancies. The purpose of this study was to identify the relationship between preoperative PDW and survival in patients with non‐small cell lung cancer (NSCLC). Methods Optimal cutoff values of PDW were confirmed using a receiver operating characteristic (ROC) curve. The Kaplan‐Meier method and log‐rank test were used to estimate disease‐free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression models were used for prognostic analysis. The likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare two models of the TNM staging system and the PDW‐TNM staging system (combination of PDW and the TNM staging system). Results Survival analysis indicated that the disease‐free survival (DFS) and overall survival (OS) of patients with PDW > 12.65 were both significantly longer than those of patients with PDW ≤ 12.65. Multivariate analysis showed that PDW was an independent prognostic factor for DFS and OS. After the two prediction models were established, further LRT analysis showed that the PDW‐TNM model had a better ability to assess patient prognosis. Conclusions PDW might act as an independent risk factor to predict progression and prognosis. Preoperative PDW combined with the TNM staging system showed a better ability to assess the prognosis of NSCLC patients. Key points Our study focused on the prognostic value of preoperative PDW in 750 patients with NSCLC. We also analyzed preoperative PDW in different stages and histological subtypes systematically. A model built by preoperative PDW combined with the TNM staging system had a better prognostic ability. LRT was used to calculate values of the goodness of fit between the model and the TNM staging system.

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“…Both platelets and megakaryocytes are able to sequester tumor‐derived proteins by endocytosis and protect cancer cells from immune clearance, which favors their adhesion to the endothelium, thus facilitating spreading . Moreover, platelets may induce a more malignant phenotype in cancer cells characterized by enhanced migratory properties …”

Section: Discussionmentioning

confidence: 99%

Preoperative monocyte‐to‐lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors

Cananzi

Minerva

Samà

et al. 2018

Journal of Surgical Oncology

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Background and Objectives: Several inflammation markers were found to have a prognostic value in cancer. We investigated the significance of preoperative white cell ratios in determining gastrointestinal stromal tumors (GISTs) outcome. Methods: Clinicopathological features of patients who underwent surgery for GIST were reviewed. The following peripheral blood inflammation markers were calculated: neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-white blood cell ratio (NWR), lymphocytewhite cell ratio (LWR), monocyte-white cell ratio (MWR), and platelet-white cell ratio (PWR). Results: We analyzed 127 patients. Three-and five-year disease-free survival (DFS) were 89.7% and 86.9%, respectively. The univariate analysis selected tumor diameter (P = 0.003), gastric location (P = 0.024), cell type (P = 0.024), mitosis (P < 0.001), MLR (P = 0.014), NLR (P = 0.016), and PLR (P = 0.001) as the factors associated to DFS. The independent prognostic factors for DFS were mitosis (P = 0.001), NLR (P = 0.015), MLR (P = 0.015), and PLR (P = 0.031), with MLR showing the highest statistical significance and hazard ratio (HR) value. MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinenʼs risk class. A high value of MLR was associated with reduced DFS. Conclusion: MLR, NLR, and PLR are independent prognostic factors for DFS in GISTs.We first demonstrated the role of MLR as a predictor of recurrence in GIST. Its inclusion into clinical management may improve the recurrence estimation.

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Platelets as crucial partners for tumor metastasis: from mechanistic aspects to pharmacological targeting

Cited by 66 publications

References 142 publications

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer

The preoperative platelet distribution width: A predictive factor of the prognosis in patients with non‐small cell lung cancer

Preoperative monocyte‐to‐lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors

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