Platelet adherence to cancer cells promotes escape from innate immune surveillance in cancer metastasis. 2020

Mitsuyoshi Okazaki, and Takahisa Yamaguchi, and Hidehiro Tajima, and Sachio Fushida, and Tetsuo Ohta
Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan.

The impacts of post‑operative abdominal infectious complications increase hematogenous distant metastasis and result in poor long‑term survival after curative resection. Even if curative resection can be performed, the presence of circulating tumor cells is affected. The liver, the most common site of metastases, is an important organ in innate immune surveillance. However, the molecular mechanisms of distant hematogenous metastasis are not yet fully known. Platelets are crucial components in the tumor microenvironment that function to promote tumor progression and metastasis. The purpose of this study was to identify the effect of platelets on escape from innate immune surveillance in post‑operative abdominal infectious complications. Platelet adherence was assessed by co‑culturing human pancreatic cancer cells including transforming growth factor (TGF‑β)‑treated BxPC‑3. CD44 isoform, transcription factors and epithelial‑mesenchymal transition markers were examined using western blotting. We also assessed whether cancer cells surrounded by activated platelets could escape from innate immune surveillance, using infectious and non‑infectious mouse models injected intraperitoneally with LPS. Platelets were found to preferentially adhere to mesenchymal cells rather than epithelial cells. BxPC‑3 epithelial cells showed upregulation of CD44‑variant and epithelial splicing regulatory protein 1 (ESRP‑1) expression. However, Panc‑1 mesenchymal cells and TGF‑β‑treated BxPC‑3 cells showed upregulation of CD44‑standard and zinc finger E‑box‑binding homeobox 1 (ZEB‑1) expression and a reduction in ESRP‑1. In the non‑infectious model, cancer cells were not found in the liver. In the infectious model, although epithelial cells without platelet adhesion were in an apoptotic state, mesenchymal cells showed many viable cancer cells surrounded by activated platelets. Cancer cells were suggested to have phenotypic plasticity through the switching of CD44 isoforms. Mesenchymal cells, which express CD44‑standard, could escape from immune surveillance by becoming surrounded by adhered activated platelets. Therefore, it may be necessary to administer antiplatelet agents to prevent distant hematogenous metastasis when post‑operative abdominal infectious complications occur.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D010973 Platelet Adhesiveness The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces. Adhesiveness, Platelet,Adhesivenesses, Platelet,Platelet Adhesivenesses
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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