Platelets: “First Responders” in Cancer Progression and Metastasis

摘要: A long-standing postulate in oncology is that platelets facilitate cancer metastasis (Menter et al. Cancer Metastasis Rev 33:231–269, 2014; Menter Invasion 7:109–128, 1987; Gasic Proc Natl Acad Sci USA 61:46–52, 1968; Woods Bulletin der Schweizerischen Akademie Medizinischen Wissenschaften 20:92–121, 1964). As their most critical biological response, serve as “first responders” during the wounding process and hemostasis. a part of metastatic process, platelet receptors recognize complexes tumor cell surface-bound matrix proteins or cellular products they invade blood vessels. This recognition triggers activation platelet-tumor interactions. Once activated by cells, change shape, degranulate, release proteins, growth factors, bioactive lipids, other factors recruit additional immune cells along with initiating thrombogenesis. Extensive membrane changes occur at bilayer interfaces between cells. Tumor form extensive membrane/cytoskeletal processes heavily interdigitate central aggregate involves uptake fragments mitochondria. These interactions are thought to result suppression recognition/cytotoxicity promotion arrest endothelium entrapment microvasculature. responses all support survival spread establishment secondary lesions. Additional mechanisms platelet-metastasis relationship may include production exosomes extravascular migratory behavior helping drive progression preconditioning sites. In contrast many involved relationships, little known about role precancerous lesion development. paucity knowledge exists despite numerous large randomized clinical trials illustrating preventive effects nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin reducing incidence, mortality, metastasis. Aspirin covalently acetylates inactivates cyclooxygenase 1 thereby eliminates downstream prostaglandin from arachidonic acid (AA) platelets. includes key lipid activation, thromboxane A2 (TxA2). Another prostaglandin, prostacyclin (PGI2), counterbalances inhibits (Honn Science 212:1270–1272, 1981). Metabolically, genesis TxA2 lipids also impacted ω-3 polyunsaturated fatty substrate substitution for AA. Although not well studied, this places only center discussion but premalignancies. Since neoangiogenesis produces leaky vessels early progression, it stands reason extravasate, activate, stroma-stimulating, proangiogenic, chemoattractive, immunomodulatory contents. normal functions undoubtedly promote series cyclic amplification events. Platelets suspected have within full spectrum continuum, which makes limiting first response an important target both prevention therapy.