Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?

Abstract

Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.

Estimation of the tissue and serum levels of IL-35 in Mycosis fungoides: a case-control study

“…Also, there was a statistically significant positive correlation between IL- 35 serum level and platelet count. This could be attributed to the active role of platelets (rich in angiogenic factors in their granules) in the tumor microenvironment (TME), being involved in tumor angiogenesis as they are rich in angiogenic factors in their granules [ 33 ]. Similarly, IL-35 promotes tumor angiogenesis and tumor cell expansion through inducing the formation of VEGF [ 6 ].…”

Preoperative Systemic Immune-Inflammation Index is a Potential Biomarker in Adult Patients with High-Grade Gliomas Undergoing Radical Resection

“…It is reported that platelets secrete pro-angiogenic cytokines, including vascular endothelial growth factor and endothelial cell growth factor, which promote tumor angiogenesis. 38,39 Furthermore, peripheral platelets facilitate the invasiveness of circulating tumor cells by covering them in a P-selectin-dependent mechanism, thereby preventing natural killer (NK) cell-mediated tumor cell apoptosis. 39 Prior researches have indicated that levels of NLR, PLR, and MLR are linked to the prognosis of patients with gliomas.…”

Research progress of megakaryocytes and platelets in lung injury

“…Megakaryocytes that migrate to the blood vessels of lung cancer tissue produce more platelets, helping tumor cells break through the endothelial barrier to achieve transendothelial migration and thus promoting the development and metastasis of lung cancer [ 64 ]. In early stage of lung cancer, increased expression of thrombospondin-1 (TSP-1) in lung megakaryocytes and platelets inhibits endogenous angiogenesis and exerts antitumor effects [ 65 ]. However, pulmonary megakaryocytes secrete platelet factor 4 (PF4), which in turn promotes hematopoietic function and megakaryocyte production under stress conditions caused by chemotherapy and radiotherapy [ 66 ], accelerating tumor growth.…”