Trends in Cancer
ReviewUndercover Agents: Targeting Tumours with Modified Platelets
Section snippets
Platelets and Malignancy: An Unavoidable Relationship
The relationship between platelets and tumour cells during haematogenous metastasis has been well studied. Mounting evidence points to tumour cell-induced platelet aggregation (TCIPA) as being a key step in aiding survival of circulating tumour cells, causing advanced disease 1, 2, 3, 4. Recently, interest in this topic has been growing and knowledge of the close interactions between these two cell types is now beginning to be exploited to aid development of targeted cancer therapies and more
Tumour-Cell-Induced Platelet Activation
Platelets and tumour cells share a relationship vital to tumour cell survival in the vasculature and subsequent haematogenous metastasis. A key process in this relationship is tumour cell-mediated activation, and subsequent aggregation, of platelets. Under normal haematological circumstances, platelets circulate in a resting state and activate in response to shear stress [21], signals from wounds in the endothelium, or nearby activated platelets [22]. However, there is now also a large body of
Platelets As Biomarkers of Cancer
As a result of the platelet activation and coagulable state induced by tumour cells, the incidence of VTE in cancer patients is high. First documented over 150 years ago [57], the hyper-reactive state of platelets induced by the cancer cells increases the risk of VTE 3–4-fold in cancer patients compared to healthy individuals, and is the second leading cause of death in cancer patients [45]. In several cancer types (for example lung, prostate, and breast) the presence of VTE is strongly
Platelets As Drug Delivery Systems
The colocalisation of platelets and tumour cells throughout haematogenous metastasis presents opportunities to manipulate this relationship for use in cancer therapies. Indeed, disruption of this relationship – through systemic depletion of platelets [4] or genetic deficiency of certain platelet adhesion molecules (e.g., P-selectin) [15] and secreted molecules (e.g., TGF-β1) [38] – elicits a significant reduction in metastatic foci in experimental models of metastasis. These methods are not
Concluding Remarks
The multifaceted interactions between tumour cells and platelets throughout the metastatic process afford numerous opportunities for the development of diagnostic tools and therapies that exploit this relationship. However, the full extent of the relationship between platelets and tumour cells is yet to be defined and questions pertaining to the possible roles of platelets in cancer progression outside of haematogenous metastasis remain unanswered (see Outstanding Questions). Cancer is a
Conflict of interest
The authors have no conflict of interest to declare.
Acknowledgements
This work was supported by grant funds received from the following: the Australian National Health and Medical Research Council Project and Program Grants (1079250, 1016647), an Independent Research Institutes Infrastructure Support Scheme Grant (9000220) and a Victorian State Government Operational Infrastructure Support Grant. E.C.J. is the recipient of a fellowship from the Galli Foundation. S.R.H. is the recipient of an Australian Postgraduate Award from the University of Melbourne. The
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2022, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :Other biological membranes may also be suitable to perform this task. Recent advances with membranes from platelets, neutrophils, natural killer cells, macrophages, stem cells, and even cancer cells warrant further studies [366–370]. As the lifespan of platelets, red blood cells, and stem cells differ profoundly, it will be interesting to determine how individual membrane coats affect NP elimination.
Recent advances in platelet engineering for anti-cancer therapies
2022, ParticuologyCitation Excerpt :In particular, novel technologies using platelets for potential cancer therapies are now being widely investigated (Hu, Fang et al., 2015). Platelets, produced by megakaryocytes, represent one type of versatile vehicle for drug delivery due to their relatively small size, lack of nucleus, and intimate role in mitigating injury to blood vessels and maintaining hemostasis through aggregation, or clumping to clot blood at the site of injuries (Hyslop & Josefsson, 2017; Yeung et al., 2018; Gaertner & Massberg, 2019). In addition, since Armand Trousseau first established the relationship between platelets and cancer metastasis, platelets have been shown to contribute central functions in cancer progression and metastasis, especially through recognition and interaction with circulating tumor cells (CTCs) in blood (Varki, 2007; Ortiz-otero et al., 2018).
Targeting transgenic proteins to alpha granules for platelet-directed gene therapy
2022, Molecular Therapy Nucleic AcidsCitation Excerpt :This unique physiology makes platelets attractive cell therapy targets. Researchers have studied the use of platelets and of platelet membrane-coated nanoparticles as drug delivery tools (e.g., to target tumors or cardiovascular disease).1–4 Platelet-directed gene therapy has been explored for the delivery of coagulation factors to treat hemophilia.5
Platelets in chronic liver disease, from bench to bedside
2019, JHEP ReportsCitation Excerpt :In turn, cancer cells can influence platelet activation and shape by releasing growth factors that bind to specific receptors on their surface (tumour “education”). Moreover, the tight communication between platelets and tumour cells, as well as their physical interactions, indicate a possible role for platelets as promising vectors for targeted drug delivery.35 Therefore, platelets take part in an intricate interplay with innate and adaptive immune responses, perpetuating inflammatory and malignant processes via various mechanisms (summarised in Fig. 2).
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