Metastatic founder cell candidates resemble preimplantation embryonic blastomeres

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 two million 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.

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BibTeX RIS

BibTeX

@misc{klein2026metastatic,
  title = {{Metastatic founder cell candidates resemble preimplantation embryonic blastomeres}},
  author = {C. A. Klein and H. Koerkel-Qu and E. Raya and M. Guzvic and C. Irlbeck and T. Mederer and D. Spitzl and Z. Czyz and L. Schunicht and S. Seitz and J. Roth and B. Rack and N. Harbeck and H. Kurdieh and R. Mayr and M. Burger and T. Robold and H.-S. Hofmann and M. Weber and M. Maak and K.-P. Janssen and S. Huecker and S. Kirsch and M. Werner-Klein and A. C. Perry},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.28.747818},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.28.747818v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Metastatic founder cell candidates resemble preimplantation embryonic blastomeres
AU  - C. A. Klein
AU  - H. Koerkel-Qu
AU  - E. Raya
AU  - M. Guzvic
AU  - C. Irlbeck
AU  - T. Mederer
AU  - D. Spitzl
AU  - Z. Czyz
AU  - L. Schunicht
AU  - S. Seitz
AU  - J. Roth
AU  - B. Rack
AU  - N. Harbeck
AU  - H. Kurdieh
AU  - R. Mayr
AU  - M. Burger
AU  - T. Robold
AU  - H.-S. Hofmann
AU  - M. Weber
AU  - M. Maak
AU  - K.-P. Janssen
AU  - S. Huecker
AU  - S. Kirsch
AU  - M. Werner-Klein
AU  - A. C. Perry
PY  - 2026
DA  - 2026/08/28
PB  - bioRxiv
DO  - 10.64898/2026.08.28.747818
UR  - https://www.biorxiv.org/content/10.64898/2026.08.28.747818v1
AB  - 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 two million 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.
ER  -

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