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Cells in the Polyaneuploid Cancer Cell State are Pro-Metastatic.
Mallin, Mikaela M; Rolle, Louis T A; Schmidt, Michael J; Nair, Shilpa Priyadarsini; Zurita, Amado J; Kuhn, Peter; Hicks, James; Pienta, Kenneth J; Amend, Sarah R.
Afiliación
  • Mallin MM; Cancer Ecology Center, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institute, Baltimore, MD, USA.
  • Rolle LTA; Cellular and Molecular Medicine Graduate Training Program, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Schmidt MJ; Cancer Ecology Center, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institute, Baltimore, MD, USA.
  • Nair SP; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
  • Zurita AJ; Cancer Ecology Center, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institute, Baltimore, MD, USA.
  • Kuhn P; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Hicks J; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
  • Pienta KJ; Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, USA.
  • Amend SR; Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
bioRxiv ; 2024 Jul 16.
Article en En | MEDLINE | ID: mdl-39071340
ABSTRACT
There remains a large need for a greater understanding of the metastatic process within the prostate cancer field. Our research aims to understand the adaptive - ergo potentially metastatic - responses of cancer to changing microenvironments. Emerging evidence has implicated a role of the Polyaneuploid Cancer Cell (PACC) state in metastasis, positing the PACC state as capable of conferring metastatic competency. Mounting in vitro evidence supports increased metastatic potential of cells in the PACC state. Additionally, our recent retrospective study of prostate cancer patients revealed that PACC presence in the prostate at the time of radical prostatectomy was predictive of future metastatic progression. To test for a causative relationship between PACC state biology and metastasis, we leveraged a novel method designed for flow-cytometric detection of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in subcutaneous, caudal artery, and intracardiac mouse models of metastasis. This approach provides both quantitative and qualitative information about the number and PACC-status of recovered CTCs and DTCs. Collating data from all models, we found that 74% of recovered CTCs and DTCs were in the PACC state. In vivo colonization assays proved PACC populations can regain proliferative capacity at metastatic sites following dormancy. Additional direct and indirect mechanistic in vitro analyses revealed a PACC-specific partial Epithelial-to-Mesenchymal-Transition phenotype and a pro-metastatic secretory profile, together providing preliminary evidence that PACCs are mechanistically linked to metastasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos