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Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.
Welter, Lisa; Zheng, Serena; Setayesh, Sonia Maryam; Morikado, Michael; Agrawal, Arushi; Nevarez, Rafael; Naghdloo, Amin; Pore, Milind; Higa, Nikki; Kolatkar, Anand; Thiele, Jana-Aletta; Sharma, Priyanka; Moore, Halle C F; Richer, Jennifer K; Elias, Anthony; Pienta, Kenneth J; Zurita, Amado J; Gross, Mitchell E; Shishido, Stephanie N; Hicks, James; Velasco, Carmen Ruiz; Kuhn, Peter.
Afiliación
  • Welter L; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Zheng S; Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
  • Setayesh SM; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Morikado M; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Agrawal A; Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
  • Nevarez R; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Naghdloo A; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Pore M; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Higa N; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Kolatkar A; Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA.
  • Thiele JA; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Sharma P; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Moore HCF; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Richer JK; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Elias A; Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Pienta KJ; University of Kansas Medical Center, Westwood, KS 66205, USA.
  • Zurita AJ; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA.
  • Gross ME; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Shishido SN; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Hicks J; The Cancer Ecology Center, Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
  • Velasco CR; Department of Genitourinary Medical Oncology, MD Anderson, Houston, TX 77230, USA.
  • Kuhn P; Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, CA 90064, USA.
Cancers (Basel) ; 15(15)2023 Aug 03.
Article en En | MEDLINE | ID: mdl-37568766
ABSTRACT
Bi-directional crosstalk between the tumor and the tumor microenvironment (TME) has been shown to increase the rate of tumor evolution and to play a key role in neoplastic progression, therapeutic resistance, and a patient's overall survival. Here, we set out to use a comprehensive liquid-biopsy analysis to study cancer and specific TME cells in circulation and their association with disease status. Cytokeratin+, CD45- circulating rare cells (CRCs) from nine breast and four prostate cancer patients were characterized through morphometrics, single-cell copy number analysis, and targeted multiplexed proteomics to delineate cancer cell lineage from other rare cells originating in the TME. We show that we can detect epithelial circulating tumor cells (EPI.CTC), CTCs undergoing epithelial-to-mesenchymal transition (EMT.CTC) and circulating endothelial cells (CECs) using a universal rare event detection platform (HDSCA). Longitudinal analysis of an index patient finds that CTCs are present at the time of disease progression, while CECs are predominately present at the time of stable disease. In a small cohort of prostate and breast cancer patients, we find high inter-patient and temporal intra-patient variability in the expression of tissue specific markers such as ER, HER2, AR, PSA and PSMA and EpCAM. Our study stresses the importance of the multi-omic characterization of circulating rare cells in patients with breast and prostate carcinomas, specifically highlighting overlapping and cell type defining proteo-genomic characteristics of CTCs and CECs.
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Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos