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Clinically Relevant Humanized Mouse Models of Metastatic Prostate Cancer Facilitate Therapeutic Evaluation.
Kostlan, Raymond J; Phoenix, John T; Budreika, Audris; Ferrari, Marina G; Khurana, Neetika; Choi, Jae E; Juckette, Kristin; Mahapatra, Somnath; McCollum, Brooke L; Moskal, Russell; Mannan, Rahul; Qiao, Yuanyuan; Vander Griend, Donald J; Chinnaiyan, Arul M; Kregel, Steven.
Afiliación
  • Kostlan RJ; Department of Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Phoenix JT; Integrated Program in Biomedical Science, Biochemistry, Molecular and Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Budreika A; Department of Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Ferrari MG; Integrated Program in Biomedical Science, Biochemistry, Molecular and Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Khurana N; Department of Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Choi JE; Integrated Program in Biomedical Science, Biochemistry, Molecular and Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Juckette K; Department of Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • Mahapatra S; Department of Cancer Biology, Loyola University Chicago, Maywood, Illinois.
  • McCollum BL; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
  • Moskal R; Department of Pathology, University of Michigan, Ann Arbor, Michigan.
  • Mannan R; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.
  • Qiao Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
  • Vander Griend DJ; Department of Pathology, University of Michigan, Ann Arbor, Michigan.
  • Chinnaiyan AM; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.
  • Kregel S; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
Mol Cancer Res ; 22(9): 826-839, 2024 Sep 04.
Article en En | MEDLINE | ID: mdl-38820127
ABSTRACT
There is tremendous need for improved prostate cancer models. Anatomically and developmentally, the mouse prostate differs from the human prostate and does not form tumors spontaneously. Genetically engineered mouse models lack the heterogeneity of human cancer and rarely establish metastatic growth. Human xenografts are an alternative but must rely on an immunocompromised host. Therefore, we generated prostate cancer murine xenograft models with an intact human immune system (huNOG and huNOG-EXL mice) to test whether humanizing tumor-immune interactions would improve modeling of metastatic prostate cancer and the impact of androgen receptor-targeted and immunotherapies. These mice maintain multiple human immune cell lineages, including functional human T-cells and myeloid cells. Implications To the best of our knowledge, results illustrate the first model of human prostate cancer that has an intact human immune system, metastasizes to clinically relevant locations, responds appropriately to standard-of-care hormonal therapies, and can model both an immunosuppressive and checkpoint-inhibition responsive immune microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Modelos Animales de Enfermedad Límite: Animals / Humans / Male Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2024 Tipo del documento: Article 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 / Modelos Animales de Enfermedad Límite: Animals / Humans / Male Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos