Platelet adherence to cancer cells promotes escape from innate immune surveillance in cancer metastasis.
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Plaquetas
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Adesividade Plaquetária
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Microambiente Tumoral
Tipo de estudo:
Prognostic_studies
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Screening_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article