Review articlePatterns and functional implications of platelets upon tumor “education”
Section snippets
Platelet physiology and bioactivity
Platelets are enucleated, disc-shaped cells with the diameter ranging 2.0–5.0 mm (White and Clawson, 1980), playing critical roles in hemostasis and thrombosis. Hemostasis is the most important physiological function of platelets, which halts bleeding after injury of blood vessels by the presence of platelet surface receptors, negatively charged cell surface, and interactions with coagulation factors (Bevers et al., 1983).
Beyond the roles in regulating hemostasis and coagulation, multiple
Platelets and cancer
It has been appreciated that, as a component of the tumor microenvironment, platelets can regulate carcinogenesis, tumor growth, tumor angiogenesis, tumor-related inflammation and tumor metastasis. Alteration of platelet numbers and functions has increasingly gained attention on cancer prevention, chemotherapy development and survival prolongation. For example, the platelet lymphocyte ratio (PLR) has been demonstrated to be invaluable in predicting cancer prognosis in the past decades (Nikolić
The ways of tumor cells “educating” platelets
The activation of platelets by tumor cells can be achieved by direct and indirect manners (Fig. 1). Direct manner indicates the straightforward contact between molecules on the membrane surface of platelets and circulating tumor cells (CTCs) (Falanga and Rickles, 1999). And here we refer “indirect” as the non-cellular contact between tumor cells and platelets.
The changes of platelets upon tumor “education”
The interactions between CTCs and platelets are reciprocal, with complicated network involved in this loop. The significant contribution of platelets to CTCs survival and tumor metastasis is nowadays well-acknowledged. However, the molecular and biochemical adaptions of platelets upon tumor “education” need to be further elucidated, which can hopefully give rise to novel therapies in cancer treatment. In the followed section, we will discuss the molecular and function changes of platelets in
Clinical applications of tumor-platelets axis
Studies on tumor-platelets axis would be helpful in tumor diagnosis, prognosis evaluation and novel anti-tumor therapy development. Due to the noninvasive advantages, “liquid biopsy” is becoming a hot topic on early diagnosis and following-up of malignancies, with platelets as one of the most studied plasma cell types. As discussed above, the tumor status can be implicated by many aspects of platelets including numerical changes, hypercoagulation activity and molecular changes. Even TCIPA is
Unanswered questions about tumor “educated” platelets
There are still several fundamental aspects to be addressed before fully illuminating tumor-platelets axis: How about the global RNA and protein changes in tumor “educated” platelets? Is the proteome and transcriptome data consistent since the platelets are anuclear? What’s the connections between multiple platelets proteins and their interplay roles in cancer? What’s the systematic platelets changes and functions in various anti-tumor therapy?
With discovery of the associations between
Conclusions
Circulating tumor cells can educate platelets by directly cell–cell interaction or indirectly via signaling molecules. Tumor cell education triggers various platelet signaling processes, such as mRNA splicing, protein expression, endocytosis and exocytosis, resulting in changes of gene and protein profiles in platelets. Investigating tumor-platelets axis is not only helpful for cancer diagnostics, but also invaluable on identifying novel drug targets.
Funding
This work was supported by the National Natural Science Foundation of China [NO. 81570078]; the Natural Science Foundation of Jiangsu Province [NO. BK20161386]; the Program of Nanjing Science and Technology of Nanjing Science and Technology Committee [No. 201605059]; and the Project of Invigorating Health Care through Science Technology and Education [Jiangsu Provincial Medical Youth Talent No. QNRC2016125].
Authors' contributions
Q. Z., P. Z. and J. Z. revised the manuscript.
T.L. and Y.S. reviewed and edited the manuscript.
All authors read and approved the final manuscript.
Acknowledgement
Thanking Bob Löwenberg for critically reading the manuscript.
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2021, BloodCitation Excerpt :This can occur through direct contact with the cells by membrane proteins or through extracellular molecules released by the cells. Interactions between platelets and cancer cells takes place through several adhesion molecules, including P-selectin, integrins, and glycoproteins present on the platelet membrane, leading to platelet responses and activation.94 On the other hand tumor cells can also release extracellular metabolites, such as proteinases (in particular thrombin), tissue factors, adenosine 5′-diphosphate, MMPs, and TXA2, that can activate platelet receptors.
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2019, BloodCitation Excerpt :The development of TEPs as a potential liquid biopsy biosource, however, is a consequence of many studies on the role of platelets in cancer over the past few centuries (Figure 1). Platelets are known for their function in coagulation of blood and wound healing, but their relationship with cancer has been studied extensively as well (reviewed in Franco et al,14 Lambert et al,15 Menter et al,16 Naderi-Meshkin and Ahmadiankia,17 Haemmerle et al,18 Olsson et al,19 Xu et al,20 Zhang et al,21 and Mancuso and Santagostino22). Two observations fundamental to the development of the concept of TEPs were made in the 19th century.
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These authors wrote the manuscript and contributed equally to this review.