The platelet contribution to cancer progression

Bambace, Nadia M.; Holmes, Chris E.

doi:10.1111/j.1538-7836.2010.04131.x

Cited by 596 publications

(535 citation statements)

References 153 publications

(157 reference statements)

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“…Preoperative PLT was negatively associated with the amount of transfused platelets during surgery (coefficient -0.49; P < 0.001), during the first week after surgery (coefficient -0.55; P < 0.001), and between 1 and 2 weeks after surgery (coefficient -0.21; P < 0.001). Accordingly, the amount of transfused platelets during surgery, during the first week after surgery, and between 1 and 2 weeks after surgery was 0 (0-6), 9 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), and 0 (0-0) units in the low platelet group and 0 (0-0), 0 (0-4), and 0 (0-0) units in the high platelet group, respectively, where 1 unit of apheresis platelets was considered to be equivalent to 6 units of platelets, as described previously. (22) Minimum PLT measured at each postoperative day during the first 2 weeks after transplantation was consistently <30 3 10 9 /L in median within the subgroup of recipients who underwent platelet transfusion on each corresponding day, indicating that platelet transfusion was performed according to our standardized protocol targeting PLT >30 3 10 9 /L (Supporting Fig.…”

Section: Association Between Perioperative Plt and Platelet Transfusionmentioning

confidence: 99%

“…(9) The relationship between platelets and tumors is not a simple epiphenomenon resulting from tumor-induced thrombopoiesis, but rather a direct contribution of platelets to multiple steps in the cancer progression, including tumor cell angiogenesis, protection from immune attack, extravasation, and arrest within the vasculature. (6,7,10,11) A previous study in hepatitis B virus (HBV) transgenic mice clearly demonstrated that antiplatelet treatment reduced intrahepatic inflammatory response and HCC development with improved longterm survival. (12) Thus, we hypothesized that the risk of HCC recurrence after living donor liver transplantation is affected by platelets.…”

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confidence: 99%

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Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

Han¹,

Lee

Yang

et al. 2017

Liver Transpl

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Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT £ 75 3 10 9 /L were matched with 97 of 119 patients who had preoperative PLT >75 3 10 9 /L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 3 10 9 /L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR] 5 3.09; 95% confidence interval [CI], 1.86-5.14; P < 0.001) and multivariate analyses (HR 5 2.10; 95% CI, 1.23-3.60; P 5 0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR 5 2.33; 95% CI, 1.36-4.01; P 5 0.002) and multivariate analyses (HR 5 1.90; 95% CI, 1.02-3.54; P 5 0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-tolymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation.Liver Transplantation 24 44-55 2018 AASLD. Liver transplantation is a well-established therapeutic option for treatment of hepatocellular carcinoma (HCC), addressing both underlying liver disease, which is considered a premalignant lesion, and tumor burden. However, many recipients experience tumor recurrence and recurrent HCC is a major cause of death. Thus, better understanding of the contributing factors for HCC metastasis will help improve liver transplant outcome. (1,2) The platelet is the primary cell for hemostasis and tissue repair, (3) but extensive experimental evidence has also illuminated the involvement of platelets in tumor growth and metastasis. (4)(5)(6) Clinical evidence has demonstrated an association between higher platelet counts (PLTs) and shorter survival time and increased recurrence after treatment in various solid tumors. (7) In terms of HCC, a retrospective analysis using a large database of biopsy-proven HCC patients reported a positive Abbrevi...

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Section: Association Between Perioperative Plt and Platelet Transfusionmentioning

confidence: 99%

mentioning

confidence: 99%

Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

Han¹,

Lee

Yang

et al. 2017

Liver Transpl

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“…The specific contribution of the platelet P2 receptors in this disease warrants further studies as the P2Y 1 receptor has also been proposed to have a role in airways inflammation [143]. Platelets are strongly involved in cancer and especially in metastatic dissemination [144,145] through complex mechanisms including the ability to mask tumour cells to the immune system and to contribute to tumoural angiogenesis. In particular, tumour cells release nucleotides which, among other stimuli, activate platelets.…”

Section: The P2y 1 Receptor As a Target For New Antiplatelet Compoundsmentioning

confidence: 99%

P2 receptors and platelet function

Hechler

Gachet

2011

Purinergic Signalling

136

127

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Following vessel wall injury, platelets adhere to the exposed subendothelium, become activated and release mediators such as TXA 2 and nucleotides stored at very high concentration in the so-called dense granules. Released nucleotides and other soluble agents act in a positive feedback mechanism to cause further platelet activation and amplify platelet responses induced by agents such as thrombin or collagen. Adenine nucleotides act on platelets through three distinct P2 receptors: two are G proteincoupled ADP receptors, namely the P2Y 1 and P2Y 12 receptor subtypes, while the P2X 1 receptor ligand-gated cation channel is activated by ATP. The P2Y 1 receptor initiates platelet aggregation but is not sufficient for a full platelet aggregation in response to ADP, while the P2Y 12 receptor is responsible for completion of the aggregation to ADP. The latter receptor, the molecular target of the antithrombotic drugs clopidogrel, prasugrel and ticagrelor, is responsible for most of the potentiating effects of ADP when platelets are stimulated by agents such as thrombin, collagen or immune complexes. The P2X 1 receptor is involved in platelet shape change and in activation by collagen under shear conditions. Each of these receptors is coupled to specific signal transduction pathways in response to ADP or ATP and is differentially involved in all the sequential events involved in platelet function and haemostasis. As such, they represent potential targets for antithrombotic drugs.

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“…5-HT has been demonstrated to have angiogenic potential. Therefore, we assessed if 5-HT could activate certain angiogenic signaling kinases.…”

Section: -Ht Activates Signaling Kinases In Human Endothelial Cellsmentioning

confidence: 99%

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

Zamani

2012

FEBS Letters

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a b s t r a c tSerotonin, a known neurotransmitter, also functions as an angiokine to promote angiogenesis. The majority of serotonin in the human body is stored in platelets, and platelet aggregation leads to significant release of serotonin in thrombotic tumor environment. We have investigated serotonin signaling in human endothelial cells. Through G-protein-coupled receptors, serotonin at physiologically relevant concentrations activated Src/PI3K/AKT/mTOR/p70S6K phosphorylation signaling, and this activation was similar to that seen with VEGF. This finding provides insight into the overlapping angiogenic signaling pathways stimulated by serotonin in tumor environment, and suggests one of the mechanisms underlying resistance to current VEGF-targeting antiangiogenic therapy against cancer.

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The platelet contribution to cancer progression

Cited by 596 publications

References 153 publications

Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

P2 receptors and platelet function

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

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