title: Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer.
abstract: Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient's prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. Characterization of cells with DNA fingerprinting demonstrated identical patterns in normal and tumor CR cells as well as in xenografted tumors. By flow cytometry, both normal and tumor CR cells expressed basal, luminal, and stem cell markers, with the majority of the normal and tumor CR cells expressing prostate basal cell markers, CD44 and Trop2, as well as luminal marker, CD13, suggesting a transit-amplifying phenotype. Consistent with this phenotype, real time RT-PCR analyses demonstrated that CR cells predominantly expressed high levels of basal cell markers (KRT5, KRT14 and p63), and low levels of luminal markers. When the CR tumor cells were injected into SCID mice, the expression of luminal markers (AR, NKX3.1) increased significantly, while basal cell markers dramatically decreased. These data suggest that CR cells maintain high levels of proliferation and low levels of differentiation in the presence of feeder cells and ROCK inhibitor, but undergo differentiation once injected into SCID mice. Genomic analyses, including SNP and INDEL, identified genes mutated in tumor cells, including components of apoptosis, cell attachment, and hypoxia pathways. The use of matched patient-derived cells provides a unique in vitro model for studies of early prostate cancer.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.|Department of Pathology and Laboratory Medicine, Lewis Katz Medical School, Temple University, Philadelphia, PA, USA.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Timofeeva
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Palechor-Ceron
authors.affiliation: Beijing Genome Research Institute, Shenzhen, Guangdong, China.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Krawczyk
authors.affiliation: Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC, USA.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Beijing Genome Research Institute, Shenzhen, Guangdong, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Geeta
authors.initials: G
authors.lastname: Upadhyay
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dakic
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Choudhury
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Medicine, Georgetown University Medical School, Washington, DC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ju
authors.affiliation: Department of Biomedical Science, Cheongju University, Sandang-Gu, Cheongju Shi Chungbuk, Republic of Korea.
authors.forename: Myeong-Seon
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Maryland, Baltimore, MD, USA.
authors.forename: Han C
authors.initials: HC
authors.lastname: Dan
authors.affiliation: Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Beijing Genome Research Institute, Shenzhen, Guangdong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.|Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Albanese
authors.affiliation: Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Johng
authors.initials: J
authors.lastname: Rhim
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Schlegel
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.|Department of Radiation Medicine, Georgetown University Medical School, Washington, DC, USA.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dritschilo
authors.affiliation: Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer cell models; cell lines; conditional cell reprogramming; patient-derived; prostate cancer