"Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma.

作者: Gary A. Clawson , Gail L. Matters , Ping Xin , Christopher McGovern , Eric Wafula

DOI: 10.1371/JOURNAL.PONE.0184451

关键词: PancreasImmunophenotypingPathologyBiologyCancerPancreatic cancerSingle-cell analysisStem cellTransplantationMetastasis

摘要: Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploidy, immunophenotypic characterizations showed that express markers characteristic PDAC stem cells, as well M2-polarized macrophages. Single RNASeq analyses many transcripts implicated in cancer progression, LINE1 retrotransposons, very high levels several long non-coding involved metastasis (such MALAT1). When cultured transplanted orthotopically into mouse pancreas, they grew obvious well-differentiated islands but also disseminated widely throughout multiple tissues "stealth" fashion. They found distributed organs at 4, 8, or 12 weeks after transplantation (including liver, spleen, lung), occurring single cells small groups without formation tumors any apparent progression over 4 to week period. We suggest form continually during development, disseminate early forming "niches" distant sites for subsequent colonization by metastasis-initiating cells.

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