Platelet “first responders” in wound response, cancer, and metastasis

Abstract

Platelets serve as “First Responders” during normal wounding and homeostasis. Arising from bone marrow stem cell lineage megakaryocytes, anucleate platelets can influence inflammation and immune regulation. Biophysically, platelets are optimized due to size and discoid morphology to distribute near vessel walls, monitor vascular integrity and initiate quick responses to vascular lesions. Adhesion receptors linked to a highly reactive filopodia-generating cytoskeleton maximizes their vascular surface contact allowing rapid response capabilities. Functionally, platelets normally initiate rapid clotting, vasoconstriction, inflammation and wound biology that leads to sterilization, tissue repair and resolution. Platelets also are among the first to sense, phagocytize, decorate, or react to pathogens in the circulation. These platelet first responder properties are commandeered during chronic inflammation, cancer progression and metastasis. Leaky or inflammatory reaction blood vessel genesis during carcinogenesis provides opportunities for platelet invasion into tumors. Cancer is thought of as a non-healing or chronic wound that can be actively aided by platelet mitogenic properties to stimulate tumor growth. This growth ultimately outstrips circulatory support leads to angiogenesis and intravasation of tumor cells into the blood stream. Circulating tumor cells reengage additional platelets, which facilitates tumor cell adhesion, arrest and extravasation and metastasis. This process, along with the hypercoagulable states associated with malignancy is amplified by IL6 production in tumors that stimulate liver thrombopoietin production and elevates circulating platelet numbers by thrombopoiesis in the bone marrow. These complex interactions and the “First Responder” role of platelets during diverse physiologic stresses provides a useful therapeutic target that deserves further exploration.

Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2

“…Hence, coagulopathy may be found in quite a lot patients with severe pneumonia. In this study, platelet count of COVID group was significantly higher than that of non-COVID group, perhaps due to the reactively increased thrombopoietin following pulmonary inflammation [12], this might mean more severe inflammation reaction and hypercoagulability in COVID group, and platelet count may not be a sensitive marker for coagulopathy of COVID-19.…”

<p>Pretreatment Systemic Inflammation Response Index in Patients with Breast Cancer Treated with Neoadjuvant Chemotherapy as a Useful Prognostic Indicator</p>

“…33,34 Platelets are an indicator of tumor activity and angiogenesis, and are associated with tumor growth, invasion, and metastasis by releasing VEGF-integrin cooperative signaling. 35,36 Moreover, lymphocytes are an important component of anticancer immunity and immune surveillance and are associated to prevent the tumor growth and progression. 37,38 Some studies have shown that inflammatory markers and immune-based prognostic indexes were used to evaluate the prognosis of breast cancer, such as NLR, d-NLR, MLR/LMR, and PLR.…”

Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling

“…Platelets are best known for their role in hemostasis,67 but their function in the immune response is an emerging research area. After antigen exposure, platelets get activated as part of the innate immune response and their activation is mediated by surface TLRs and danger signal lipopolysaccharides 68, 69, 70.…”

“…65,66 Tfregs may also inhibit B cell activity by disrupting the mechanical interaction between T cells and B cells. 66 Feedback and feedforward regulation by platelets Platelets are best known for their role in hemostasis, 67 but their function in the immune response is an emerging research area. After antigen exposure, platelets get activated as part of the innate immune response and their activation is mediated by surface TLRs and danger signal lipopolysaccharides.…”