"Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma
Open Access
- 28 September 2017
- journal article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 12 (9), e0184451
- https://doi.org/10.1371/journal.pone.0184451
Abstract
Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploidy, and immunophenotypic characterizations showed that the MTFs express markers characteristic of PDAC and stem cells, as well as M2-polarized macrophages. Single cell RNASeq analyses showed that the MTFs express many transcripts implicated in cancer progression, LINE1 retrotransposons, and very high levels of several long non-coding transcripts involved in metastasis (such as MALAT1). When cultured MTFs were transplanted orthotopically into mouse pancreas, they grew as obvious well-differentiated islands of cells, but they also disseminated widely throughout multiple tissues in “stealth” fashion. They were found distributed throughout multiple organs at 4, 8, or 12 weeks after transplantation (including liver, spleen, lung), occurring as single cells or small groups of cells, without formation of obvious tumors or any apparent progression over the 4 to 12 week period. We suggest that MTFs form continually during PDAC development, and that they disseminate early in cancer progression, forming “niches” at distant sites for subsequent colonization by metastasis-initiating cells.Keywords
Funding Information
- National Center for Advancing Translational Sciences (UL1 TR000125)
- National Institutes of Health (1S10OD010756-01A1)
- National Institutes of Health (1S10OD018124-01A1)
- Gittlen Cancer Research Laboratories
This publication has 183 references indexed in Scilit:
- Epithelial–mesenchymal transition markers expressed in circulating tumor cells in hepatocellular carcinoma patients with different stages of diseaseCell Death & Disease, 2013
- B4GALT family mediates the multidrug resistance of human leukemia cells by regulating the hedgehog pathway and the expression of p-glycoprotein and multidrug resistance-associated protein 1Cell Death & Disease, 2013
- DRAM1 Regulates Autophagy Flux through LysosomesPLOS ONE, 2013
- Lentivirus‐Mediated RNAi Knockdown of NUPR1 Inhibits Human Nonsmall Cell Lung Cancer Growth In Vitro and In VivoThe Anatomical Record, 2012
- Homotypic cell cannibalism, a cell‐death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancerEMBO Molecular Medicine, 2012
- EMT and Dissemination Precede Pancreatic Tumor FormationCell, 2012
- Inhibition of MIF Leads to Cell Cycle Arrest and Apoptosis in Pancreatic Cancer CellsJournal of Surgical Research, 2010
- SOSS Complexes Participate in the Maintenance of Genomic StabilityMolecular Cell, 2009
- Interferon‐inducible protein IFIXα inhibits cell invasion by upregulating the metastasis suppressor maspinMolecular Carcinogenesis, 2008
- Chapter 10 The Cancer Cell–Leukocyte Fusion Theory of MetastasisAdvances in Cancer Research, 2008