Metastatic founder cell candidates resemble preimplantation embryonic blastomeres
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Disseminated cancer cells (DCC) in non-metastatic carcinoma patient bone marrow (BM) are predictive of metastasis. Those detected by epithelial cytokeratin or EpCAM expression have poorly-characterized transcription profiles due to their extreme rarity: 1∼2 cells per 2x 10 6 BM cells in every third non-metastatic patient. We here characterize the transcriptomes of DCCs. Single-cell RNA-sequencing (scRNA-seq) of 864 EpCAM-positive cells (from 1,151 cancer patients) in BM or lymph nodes (LN) revealed plasma, immune, myeloid, erythroid progenitor cells and two candidate DCC populations, termed M0-DCC and M1-DCC. M0-DCC, mostly from non-metastatic M0-stage patients, displayed the highest known adult stemness scores, and were transcriptomically reminiscent of human cleavage-stage, preimplantation embryos. M1-DCC represented cancer cells undergoing the epithelial-mesenchymal transition (EMT), corresponding to later, implanting and gastrulating embryos. Detection of early-embryo-like DCC categorised patients at highest risk for metastatic progression. Furthermore, high M0-DCC scores predicted the metastatic potential of human cell lines from the Cancer Cell Line Encyclopedia. M0-DCC gene expression profiles can be reversibly induced from M1-DCC-like cells in vitro . The close correspondence between gene expression profiles in immediate early embryonic development and metastatic founder cell candidates provides strong evidence that the onset of cancer and metastasis recruits mechanisms employed in fertilization.
Authors: Huiqin Körkel-Qu, Elia Raya, Miodrag Guzvic, Christoph Irlbeck, Tobias Mederer, Daniel Spitzl, Zbigniew Czyz, Leon Schunicht, Stephan Seitz, Jonas Roth, Brigitte Rack, Nadia Harbeck, Hasan Kurdieh, Roman Mayr, Max Burger, Tobias Robold, Hans-Stefan Hofmann, Markus Weber, Matthias Maak, Klaus-Peter Janssen, Sarah Hücker, Stefan Kirsch, Melanie Werner-Klein, Anthony C.F Perry, Christoph A. Klein
Institutions: University Hospital Regensburg, Caritas-Krankenhaus St. Josef, University of Regensburg, Fraunhofer Institute for Toxicology and Experimental Medicine, University Hospital Ulm, LMU Klinikum, Ludwig-Maximilians-Universität München, Krankenhaus Barmherzige Brüder, TUM Klinikum, Technical University of Munich, University of Bath
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Deutsche Krebshilfe
Award: G1387417213
OpenAlex ID: W7204808446