title: Dissociated primary human prostate cancer cells coinjected with the immortalized Hs5 bone marrow stromal cells generate undifferentiated tumors in NOD/SCID-γ mice.
abstract: Reconstitution of tumor development in immunodeficient mice from disaggregated primary human tumor cells is always challenging. The main goal of the present study is to establish a reliable assay system that would allow us to reproducibly reconstitute human prostate tumor regeneration in mice using patient tumor-derived single cells. Using many of the 114 untreated primary human prostate cancer (HPCa) samples we have worked on, here we show that: 1) the subcutaneum represents the most sensitive site that allows the grafting of the implanted HPCa pieces; 2) primary HPCa cells by themselves fail to regenerate tumors in immunodeficient hosts; 3) when coinjected in Matrigel with rUGM (rat urogenital sinus mesenchyme), CAF (carcinoma-associated fibroblasts), or Hs5 (immortalized bone marrow derived stromal) cells, primary HPCa cells fail to initiate serially transplantable tumors in NOD/SCID mice; and 4) however, HPCa cells coinjected with the Hs5 cells into more immunodeficient NOD/SCID-IL2Rγ(-/-) (NSG) mice readily regenerate serially transplantable tumors. The HPCa/Hs5 reconstituted 'prostate' tumors present an overall epithelial morphology, are of the human origin, and contain cells positive for AR, CK8, and racemase. Cytogenetic analysis provides further evidence for the presence of karyotypically abnormal HPCa cells in the HPCa/Hs5 tumors. Of importance, HPCa/Hs5 xenograft tumors contain EpCAM(+) cells that are both clonogenic and tumorigenic. Surprisingly, all HPCa/Hs5 reconstituted tumors are undifferentiated, even for HPCa cells derived from Gleason 7 tumors. Our results indicate that primary HPCa cells coinjected with the immortalized Hs5 stromal cells generate undifferentiated tumors in NSG mice and we provide evidence that undifferentiated HPCa cells might be the cells that possessed tumorigenic potential and regenerated HPCa/Hs5 xenograft tumors.
authors: Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.
authors: Xin
authors: X
authors: Chen
authors: Bigang
authors: B
authors: Liu
authors: Qiuhui
authors: Q
authors: Li
authors: Sofia
authors: S
authors: Honorio
authors: Xin
authors: X
authors: Liu
authors: Can
authors: C
authors: Liu
authors: Asha S
authors: AS
authors: Multani
authors: Tammy
authors: T
authors: Calhoun-Davis
authors: Dean G
authors: DG
authors: Tang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous