Hypoxia exosome derived CEACAM5 promotes tumor-associated macrophages M2 polarization to accelerate pancreatic neuroendocrine tumors metastasis via MMP9.
FASEB J
; 38(13): e23762, 2024 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-38923643
ABSTRACT
Exosomes play significant roles in the communications between tumor cells and tumor microenvironment. However, the specific mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic neuroendocrine tumors (pNETs) are not well understood. This study aims to investigate these mechanisms and made several important discoveries. We found that hypoxic exosomes derived from pNETs cells can activate tumor-associated macrophages (TAM) to the M2 phenotype, in turn, the M2-polarized TAM, facilitate the migration and invasion of pNETs cells. Further investigation revealed that CEACAM5, a protein highly expressed in hypoxic pNETs cells, is enriched in hypoxic pNETs cell-derived exosomes. Hypoxic exosomal CEACAM5 was observed to induce M2 polarization of TAM through activation of the MAPK signaling pathway. Coculturing pNETs cells with TAM or treated with hypoxic exosomes enhanced the metastatic capacity of pNETs cells. In conclusion, these findings suggest that pNETs cells generate CEACAM5-rich exosomes in a hypoxic microenvironment, which in turn polarize TAM promote malignant invasion of pNETs cells. Targeting exosomal CEACAM5 could potentially serve as a diagnostic and therapeutic strategy for pNETs.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Antígenos CD
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Tumores Neuroendócrinos
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Metaloproteinase 9 da Matriz
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Exossomos
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Proteínas Ligadas por GPI
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Microambiente Tumoral
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Macrófagos Associados a Tumor
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article