title: Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors.
abstract: Patient-derived xenograft (PDX) tumor models have emerged as a new approach to evaluate the effects of cancer drugs on patients' personalized tumor grafts enabling to select the best treatment for the cancer patient and providing a new tool for oncology drug developers. Here, we report that human tumors engrafted in immunodeficient mice are susceptible to formation of B-and T-cell PDX tumors. We xenografted human primary and metastatic tumor samples into immunodeficient mice and found that a fraction of PDX tumors generated from patients' samples of breast, colon, pancreatic, bladder and renal cancer were histologically similar to lymphocytic neoplasms. Moreover, we found that the first passage of breast and pancreatic cancer PDX tumors after initial transplantation of the tumor pieces from the same human tumor graft could grow as a lymphocytic tumor in one mouse and as an adenocarcinoma in another mouse. Whereas subcutaneous PDX tumors resembling human adenocarcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphocytic tumors were fast growing and formed large metastatic lesions in mouse lymph nodes, liver, lungs, and spleen. PDX lymphocytic tumors were comprised of B-cells which were Epstein-Barr virus positive and expressed CD45 and CD20. Because B-cells are typically present in malignant solid tumors, formation of B-cell tumor may evolve in a wide range of PDX tumor models. Although PDX tumor models show great promise in the development of personalized therapy for cancer patients, our results suggest that confidence in any given PDX tumor model requires careful screening of lymphocytic markers.
authors.affiliation: Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 2170 Campus Drive, Evanston, IL, USA; Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL, USA.
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Bondarenko
authors.affiliation: Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 2170 Campus Drive, Evanston, IL, USA; Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Ugolkov
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, 60611, IL, USA; Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 710 North Fairbanks Court, Chicago, IL, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rohan
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, 60611, IL, USA; Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 710 North Fairbanks Court, Chicago, IL, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulesza
authors.affiliation: Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 2170 Campus Drive, Evanston, IL, USA; Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL, USA.
authors.forename: Oleksii
authors.initials: O
authors.lastname: Dubrovskyi
authors.affiliation: Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 710 North Fairbanks Court, Chicago, IL, USA.
authors.forename: Demirkan
authors.initials: D
authors.lastname: Gursel
authors.affiliation: Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 710 North Fairbanks Court, Chicago, IL, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Mathews
authors.affiliation: Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL, USA.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, 60611, IL, USA; Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 710 North Fairbanks Court, Chicago, IL, USA.
authors.forename: Jian J
authors.initials: JJ
authors.lastname: Wei
authors.affiliation: Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 2170 Campus Drive, Evanston, IL, USA; Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 320 East Superior Street, Chicago, 60611, IL, USA; Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL, USA. Electronic address: a-mazar@northwestern.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mazar
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008223:Lymphoma / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D051379:Mice; D014183:Transplantation, Heterologous / Q000379:methods; D023041:Xenograft Model Antitumor Assays / Q000379:methods*