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Platelet adherence to cancer cells promotes escape from innate immune surveillance in cancer metastasis.
Okazaki, Mitsuyoshi; Yamaguchi, Takahisa; Tajima, Hidehiro; Fushida, Sachio; Ohta, Tetsuo.
Afiliação
  • Okazaki M; Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920­8641, Japan.
  • Yamaguchi T; Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920­8641, Japan.
  • Tajima H; Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920­8641, Japan.
  • Fushida S; Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920­8641, Japan.
  • Ohta T; Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920­8641, Japan.
Int J Oncol ; 57(4): 980-988, 2020 10.
Article em En | MEDLINE | ID: mdl-32945350
The impacts of post­operative abdominal infectious complications increase hematogenous distant metastasis and result in poor long­term 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 post­operative abdominal infectious complications. Platelet adherence was assessed by co­culturing human pancreatic cancer cells including transforming growth factor (TGF­ß)­treated BxPC­3. CD44 isoform, transcription factors and epithelial­mesenchymal 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 non­infectious mouse models injected intraperitoneally with LPS. Platelets were found to preferentially adhere to mesenchymal cells rather than epithelial cells. BxPC­3 epithelial cells showed upregulation of CD44­variant and epithelial splicing regulatory protein 1 (ESRP­1) expression. However, Panc­1 mesenchymal cells and TGF­ß­treated BxPC­3 cells showed upregulation of CD44­standard and zinc finger E­box­binding homeobox 1 (ZEB­1) expression and a reduction in ESRP­1. In the non­infectious 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 CD44­standard, 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 post­operative abdominal infectious complications occur.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Plaquetas / Adesividade Plaquetária / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Screening_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Plaquetas / Adesividade Plaquetária / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Screening_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article