Open AccessEstablishment of a dog primary prostate cancer organoid using the urine cancer stem cells
Author(s) -
Usui Tatsuya,
Sakurai Masashi,
Nishikawa Shimpei,
Umata Koji,
Nemoto Yuki,
Haraguchi Tomoya,
Itamoto Kazuhito,
Mizuno Takuya,
Noguchi Shunsuke,
Mori Takashi,
Iwai Satomi,
Nakagawa Takayuki,
Yamawaki Hideyuki,
Ohama Takashi,
Sato Koichi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13418
Subject(s) - organoid , stem cell , biology , stem cell marker , cancer research , pathology , microbiology and biotechnology , medicine
Dog spontaneously develop prostate cancer ( PC ) like humans. Because most dogs with PC have a poor prognosis, they could be used as a translational model for advanced PC in humans. Stem cell‐derived 3‐D organoid culture could recapitulate organ structures and physiology. Using patient tissues, a human PC organoid culture system was established. Recent study has shown that urine cells also possess the characteristic of stem cells. However, urine cell‐derived PC organoids have never been produced. Therefore, we generated PC organoids using the dog urine samples. Urine organoids were successfully generated from each dog with PC . 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, CK 5, and a luminal cell marker, CK 8. CD 49f‐sorted basal cell organoids rapidly grew compared with CD 24‐sorted luminal cell organoids. The population of CD 44‐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 an mTOR inhibitor, rapamycin, decreased the cell viability of organoids. Treatment with a Hedgehog signal inhibitor, GANT 61, increased the radiosensitivity in the organoids. These findings revealed that PC organoids using urine might become a useful tool for investigating the mechanisms of the pathogenesis and treatment of PC in dogs.