PMID- 36816969
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230224
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - mTOR pathway as a potential therapeutic target for cancer stem cells in canine 
      mammary carcinoma.
PG  - 1100602
LID - 10.3389/fonc.2023.1100602 [doi]
LID - 1100602
AB  - Mammary adenocarcinoma, the most common cancer in female dogs, often exhibits the 
      lymph node and lung metastases and has a higher mortality rate. However, mammary 
      adenocarcinoma has no established treatment, except early surgical excision. 
      Canine mammary carcinoma has many common features with human mammary carcinoma, 
      including clinical characteristics, heterogeneity, and genetic aberrations, 
      making it an excellent spontaneous tumor model for human breast cancer. Diverse 
      cancers comprised heterogeneous cell populations originating from cancer stem 
      cells (CSCs) with self-renewal ability. Therefore, in addition to conventional 
      therapy, therapeutic strategies targeting CSCs are essential for cancer 
      eradication. The present study aimed to extract inhibitors of canine mammary CSCs 
      that suppress their self-renewal ability. Sphere-formation assay, which evaluates 
      self-renewal ability, was performed for the canine mammary cancer cell lines CTBp 
      and CNMp. The spheres formed in this assay were used in inhibitor library 
      screening, which identified various signaling pathways such as proteosome, stress 
      inducer, and mammalian target of rapamycin (mTOR). The present study focused on 
      the mTOR signaling pathway. Western blotting showed higher levels of 
      phosphorylated mTOR in sphere-forming CTBp and CNMp cells than in adherent cells. 
      Drug sensitivity examination using the mTOR inhibitors everolimus and 
      temsirolimus revealed dose-dependent reductions in viability among both 
      sphere-forming cells and adherent cells. Expression of phosphorylated mTOR in 
      adherent and sphere-forming cells decreased by everolimus and temsirolimus 
      treatment. In mice transplanted with CTBp-derived spheres, everolimus treatment 
      significantly decreased tumor volume compared to control. These results reveal 
      that the mTOR signaling pathway may be a potential to be a therapeutic target in 
      both cancer cells and CSCs. Novel therapeutic strategies for canine mammary 
      carcinoma are expected to benefit to human breast carcinoma as well.
CI  - Copyright (c) 2023 Michishita, Ochiai, Nakahira, Azakami, Machida, Nagashima, 
      Nakagawa and Ishiwata.
FAU - Michishita, Masaki
AU  - Michishita M
AD  - Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon 
      Veterinary and Life Science University, Tokyo, Japan.
AD  - Research Center for Animal Life Science, Nippon Veterinary and Life Science 
      University, Tokyo, Japan.
FAU - Ochiai, Kazuhiko
AU  - Ochiai K
AD  - Research Center for Animal Life Science, Nippon Veterinary and Life Science 
      University, Tokyo, Japan.
AD  - Department of Veterinary Hygiene, Faculty of Veterinary Science, Nippon 
      Veterinary and Life Science University, Tokyo, Japan.
FAU - Nakahira, Rei
AU  - Nakahira R
AD  - Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon 
      Veterinary and Life Science University, Tokyo, Japan.
FAU - Azakami, Daigo
AU  - Azakami D
AD  - Laboratory of Veterinary Clinical Oncology, Faculty of Agriculture, Tokyo 
      University of Agriculture and Technology, Tokyo, Japan.
FAU - Machida, Yukino
AU  - Machida Y
AD  - Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon 
      Veterinary and Life Science University, Tokyo, Japan.
FAU - Nagashima, Tomokazu
AU  - Nagashima T
AD  - Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon 
      Veterinary and Life Science University, Tokyo, Japan.
FAU - Nakagawa, Takayuki
AU  - Nakagawa T
AD  - Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life 
      Science, The University of Tokyo, Tokyo, Japan.
FAU - Ishiwata, Toshiyuki
AU  - Ishiwata T
AD  - Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 
      Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230127
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9931192
OTO - NOTNLM
OT  - cancer stem cells (CSC)
OT  - dog
OT  - mTOR
OT  - mammary adenocarcinoma
OT  - sphere-formation assay
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/02/24 06:00
MHDA- 2023/02/24 06:01
PMCR- 2023/01/01
CRDT- 2023/02/23 09:29
PHST- 2022/11/17 00:00 [received]
PHST- 2023/01/16 00:00 [accepted]
PHST- 2023/02/23 09:29 [entrez]
PHST- 2023/02/24 06:00 [pubmed]
PHST- 2023/02/24 06:01 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1100602 [doi]
PST - epublish
SO  - Front Oncol. 2023 Jan 27;13:1100602. doi: 10.3389/fonc.2023.1100602. eCollection 
      2023.