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Live cell molecular analysis of primary prostate cancer organoids identifies persistent androgen receptor signaling.
Heninger, Erika; Kosoff, David; Rodems, Tamara S; Sethakorn, Nan; Singh, Anupama; Gungurthi, Harshitha; Carlson, Kristin N; Yang, Bing; Gilsdorf, Cole; Pasch, Cheri A; Deming, Dustin A; Ellis, Leigh; Beebe, David J; Jarrard, David F; Lang, Joshua M.
Afiliación
  • Heninger E; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Kosoff D; Department of Medicine, University of Wisconsin, Madison, 1111 Highland Ave., Madison, WI, 53705, USA.
  • Rodems TS; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Sethakorn N; Department of Medicine, University of Wisconsin, Madison, 1111 Highland Ave., Madison, WI, 53705, USA.
  • Singh A; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Gungurthi H; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Carlson KN; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Yang B; Department of Urology, 1111 Highland Ave., Madison, WI, 53705, USA.
  • Gilsdorf C; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Pasch CA; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA.
  • Deming DA; Department of Medicine, University of Wisconsin, Madison, 1111 Highland Ave., Madison, WI, 53705, USA.
  • Ellis L; Division of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
  • Beebe DJ; Department of Pathology and Laboratory Medicine, 1111 Highland Ave., Madison, WI, 53705, USA.
  • Jarrard DF; Department of Urology, 1111 Highland Ave., Madison, WI, 53705, USA.
  • Lang JM; University of Wisconsin Carbone Cancer Center, 1111 Highland Ave., Madison, USA. jmlang@medicine.wisc.edu.
Med Oncol ; 38(11): 135, 2021 Sep 28.
Article en En | MEDLINE | ID: mdl-34581895
Prostate Cancer (PC) is a disease with remarkable tumor heterogeneity that often manifests in significant intra-patient variability with regards to clinical outcomes and treatment response. Commonly available PC cell lines do not accurately reflect the complexity of this disease and there is critical need for development of new models to recapitulate the intricate hierarchy of tumor pathogenesis. In current study, we established ex vivo primary patient-derived cancer organoid (PDCO) cultures from prostatectomy specimens of patients with locally advanced PC. We then performed a comprehensive multi-parameter characterization of the cellular composition utilizing a novel approach for live-cell staining and direct imaging in the integrated microfluidic Stacks device. Using orthogonal flow cytometry analysis, we demonstrate that primary PDCOs maintain distinct subsets of epithelial cells throughout culture and that these cells conserve expression of androgen receptor (AR)-related elements. Furthermore, to confirm the tumor-origin of the PDCOs we have analyzed the expression of PC-associated epigenetic biomarkers including promoter methylation of the GSTP1, RASSF1 and APC and RARb genes by employing a novel microfluidic rare-event screening protocol. These results demonstrate that this ex vivo PDCO model recapitulates the complexity of the epithelial tumor microenvironment of multifocal PC using orthogonal analyses. Furthermore, we propose to leverage the Stacks microfluidic device as a high-throughput, translational platform to interrogate phenotypic and molecular endpoints with the capacity to incorporate a complex tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Organoides / Receptores Androgénicos Tipo de estudio: Guideline Límite: Humans / Male Idioma: En Revista: Med Oncol Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Organoides / Receptores Androgénicos Tipo de estudio: Guideline Límite: Humans / Male Idioma: En Revista: Med Oncol Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos