Open Access"Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma
Author(s) -
Gary A. Clawson,
Gail L. Matters,
Ping Xin,
Christopher McGovern,
Eric Wafula,
Claude W. dePamphilis,
Morgan Meckley,
Joyce Y. Wong,
Luke A. Stewart,
Christopher D’Jamoos,
Н. Д. Альтман,
Yuka Imamura Kawasawa,
Zhaohui Du,
Loren Honaas,
Thomas Abraham
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184451
Subject(s) - metastasis , biology , pathology , malat1 , pancreatic cancer , cancer research , adenocarcinoma , stem cell , tumor progression , pancreas , transplantation , cancer , medicine , downregulation and upregulation , microbiology and biotechnology , gene , long non coding rna , biochemistry , genetics
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.