Contribution of platelets to tumour metastasis

Felding-Habermann, Brunhilde

doi:10.1038/nrc3004

Cited by 1,415 publications

(1,276 citation statements)

References 159 publications

(181 reference statements)

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“…The abundant platelets significantly assist tumor metastasis 12, 13, 14, 15, 16. To explore the adhesion between tumor cells and platelets in vitro, platelets were extracted from the blood of male C57BL/6 mice, labeled with calcein AM, and coincubated for 30 min with B16F10 cells treated with PBS, LMWH, LT NPs, or PLT NPs.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

Long

Mei

et al. 2018

Advanced Science

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Metastasis remains the main driver of mortality in patients suffering from cancer because of the refractoriness resulting from the multi‐phase metastatic cascade. Herein, a multifunctional self‐delivering PBA‐LMWH‐TOS nanoparticle (PLT NP) is established that acts as both nanocarrier and anti‐metastatic agent with effects on most hematogenous metastases of cancers. The hydrophilic segment (low molecular weight heparin, LMWH) inhibits the interactions between tumor cells and platelets. The hydrophobic segment (d‐α‐tocopheryl succinate, TOS) could inhibit the expression of matrix metalloproteinase‐9 (MMP‐9) in B16F10 cells which is first reported in this article. Surprisingly, even the blank NPs showed excellent anti‐metastatic capacity in three mouse models by acting on different phases of the metastatic cascade. Moreover, the overexpression of sialic acid (SA) residues on tumor cells is implicated in the malignant and metastatic phenotypes of cancers. Thus, these 3‐aminophenylboronic acid (PBA)‐modified doxorubicin (DOX)‐loaded NPs offer an efficient approach for the treatment of both solid melanomas and metastases. Furthermore, a simple pH‐sensitive “Fructose (Fru)‐blocking” coping strategy is established to reduce the NP distribution in normal tissues and distinctly increases the accumulation in melanoma tumors. These micellar NPs consisting of biocompatible materials offer a promising approach for the clinical therapy of highly invasive solid tumors and metastases.

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Section: Resultsmentioning

confidence: 99%

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

Long

Mei

et al. 2018

Advanced Science

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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

138

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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“…Cancer patients often present with changed coagulation parameters, increased platelet turnover, and various forms of thrombosis, whose severity correlate with the progress of the metastatic stage. The detailed mechanisms behind these observations have remained unclear, but recent findings have stimulated a renewed focus onto the involvement of platelets in tumor development and growth (for reviews, see [2] [3] [4] ). Even the growth of very small tumors (< 1mm 3 ) is dependent on neovasculature development [5] .…”

Section: Introductionmentioning

confidence: 99%

Fluorescence Nanoscopy of Platelets Resolves Platelet‐State Specific Storage, Release and Uptake of Proteins, Opening up Future Diagnostic Applications

Rönnlund¹,

Yang²,

Blom³

et al. 2012

Adv Healthcare Materials

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Abstract:Dysregulation of how platelets store, sequester and release specific proteins seems to be implicated in many disease states, including cancer. Dual-color immunofluorescence stimulated emission depletion (STED) microscopy with 40 nm resolution was used to map pro-angiogenic VEGF, anti-angiogenic PF-4 and fibrinogen in more than 300 individual platelets. This imaging technique, offering distinct resolving advantages for protein localization studies in platelets, reveals that these proteins are stored in a segmented, zonal manner within regional clusters, significantly smaller than the size of an -granule. No co-localization between the different proteins could be observed. Moreover, upon platelet activation by thrombin or ADP, the proteins were found to undergo significant spatial rearrangements, including alterations in the size and number of the protein clusters, which were specific for a certain protein and the type of activation induced. Following these observations, we devised a simple assignment procedure, showing that the three distinct states of platelets (non-, ADP-and thrombin-activated) can be identified based on the average size, number and peripheral localization profiles of the regional protein clusters within the platelets. This suggests that high-resolution spatial mapping in platelets of specific proteins is a useful procedure to detect and characterize deviations in the selective storage, release and uptake of these proteins in the platelets. Since these deviations seem to be specific for, and may even underlie certain patophysiological states including cancer, these findings may have interesting diagnostic and even therapeutic implications.3

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Contribution of platelets to tumour metastasis

Cited by 1,415 publications

References 159 publications

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

P2 receptors and platelet function

Fluorescence Nanoscopy of Platelets Resolves Platelet‐State Specific Storage, Release and Uptake of Proteins, Opening up Future Diagnostic Applications

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