title: Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells.
abstract: Patient derived xenograft (PDX) models are gaining popularity in cancer research and are used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. Circulating tumor cells (CTC) play a critical role in tumor metastasis and have been isolated from patients with several tumor types. Recently, CTCs have been used to generate PDX experimental models of breast and prostate cancer. This manuscript details the method for the generation of prostate cancer PDX models from CTCs developed by our group. Advantages of this method over conventional PDX models include independence from surgical sample collection and generating experimental models at various disease stages. Density gradient centrifugation followed by red blood cell lysis and flow cytometry depletion of CD45 positive mononuclear cells is used to enrich CTCs from peripheral blood samples collected from patients with metastatic disease. The CTCs are then injected into immunocompromised mice; subsequently generated xenografts can be used for functional studies or harvested for molecular characterization. The primary limitation of this method is the negative selection method used for CTC enrichment. Despite this limitation, the generation of PDX models from CTCs provides a novel experimental model to be applied to prostate cancer research.
authors.affiliation: Department of Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: Estrelania S
authors.initials: ES
authors.lastname: Williams
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center.
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodriguez-Bravo
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodriquez-Bravo
authors.affiliation: Department of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: Uma
authors.initials: U
authors.lastname: Chippada-Venkata
authors.affiliation: Department of Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: Janis
authors.initials: J
authors.lastname: De Ia Iglesia-Vicente
authors.affiliation: Department of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: Matthew
authors.initials: M
authors.lastname: Galsky
authors.affiliation: Department of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: William
authors.initials: W
authors.lastname: Oh
authors.affiliation: Department of Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.affiliation: Department of Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai; josep.domingo-domenech@mssm.edu.
authors.forename: Josep
authors.initials: J
authors.lastname: Domingo-Domenech
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D002452:Cell Count; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human