Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells

• DOI: 10.1111/cas.13418
• Publication Date: 2017-10-10T14:58:43Z
• Authors: Tatsuya Usui; Masashi Sakurai; Shimpei Nishikawa; Koji Umata; Yuki Nemoto; Tomoya Haraguchi; Kazuhito Itamoto; Takuya Mizuno; Shunsuke Noguchi; Takashi Mori; Satomi Iwai; Takayuki Nakagawa; Hideyuki Yamawaki; Takashi Ohama; Koichi Sato
• Keywords: Male; 0301 basic medicine; Cell Culture Techniques; Prostatic Neoplasms; Original Articles; Mice, SCID; Urine; 6. Clean water; 3. Good health; Organoids; Disease Models, Animal; Mice; 03 medical and health sciences; Dogs; Mice, Inbred NOD; Neoplastic Stem Cells; Animals; Heterografts

Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs withPChave a poor prognosis, they could be used as a translational model for advancedPCin humans. Stem cell‐derived 3‐D organoid culture could recapitulate organ structures and physiology. Using patient tissues, a humanPCorganoid culture system was established. Recent study has shown that urine cells also possess the characteristic of stem cells. However, urine cell‐derivedPCorganoids have never been produced. Therefore, we generatedPCorganoids using the dog urine samples. Urine organoids were successfully generated from each dog withPC. Each organoid showed cystic structures and resembled the epithelial structures of original tissues. Expression of an epithelial cell marker, E‐cadherin, and a myofibloblast marker, α‐SMA, was observed in the urine organoids. The organoids also expressed a basal cell marker,CK5, and a luminal cell marker,CK8.CD49f‐sorted basal cell organoids rapidly grew compared withCD24‐sorted luminal cell organoids. The population ofCD44‐positive cells was the highest in both organoids and the original urine cells. Tumors were successfully formed with the injection of the organoids into immunodeficient mice. Treatment with a microtubule inhibitor, docetaxel, but not a cyclooxygenase inhibitor, piroxicam, and anmTORinhibitor, rapamycin, decreased the cell viability of organoids. Treatment with a Hedgehog signal inhibitor,GANT61, increased the radiosensitivity in the organoids. These findings revealed thatPCorganoids using urine might become a useful tool for investigating the mechanisms of the pathogenesis and treatment ofPCin dogs.