Small extracellular vesicles miR-183-5p derived from highly invasive pancreatic neuroendocrine tumors reprogram macrophages towards SPP1+ macrophages

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Introduction: Highly-metastatic (HM) pancreatic neuroendocrine tumors (pNETs) are characterized by an early occurrence of lymph node and liver metastases and a poor prognosis. Single-cell sequencing analysis showed that HM pNETs had remarkable infiltration of SPP1+ macrophages, which were involved in cell migration, angiogenesis and small extracellular vesicles (sEVs).

Aim(s): This study aims to explore the underlying mechanisms of sEVs-mediated cell communication led to promote tumor progression.

Materials and methods: Multiplexed immunofluorescence staining was used to evaluate the prognostic value of SPP1+ macrophages in a patient cohort. HM cells were established by transwell assays, and the sEVs were isolated and subjected to small RNA sequencing. Animal studies including Matrigel plug assays, subcutaneous xenograft, and popliteal lymphatic metastasis assays were performed. Peritoneal macrophages were isolated from SPP1-knockout C57BL/6N mice.

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Authors: Zhang W, Xu J, Lou X, Qin Y, Chen J,

Keywords: pancreatic neuroendocrine tumor, p53, small extracellular vesicles, macrophages, SPP1, biomarker,