PMID- 31954695
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20201109
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 388
IP  - 2
DP  - 2020 Mar 15
TI  - CD44 variant 6 is associated with prostate cancer growth and chemo-/radiotherapy 
      response in vivo.
PG  - 111850
LID - S0014-4827(20)30044-6 [pii]
LID - 10.1016/j.yexcr.2020.111850 [doi]
AB  - We have previously demonstrated that CD44 variant 6 (CD44v6) is associated with 
      prostate cancer (CaP) growth and therapeutic resistance in vitro, however, the 
      role of CD44v6 in CaP in vivo is not fully understood. The purpose of this study 
      is to investigate the effect of CD44v6 on CaP growth and chemo-/radiotherapy 
      response in NOD/SCID mouse models in vivo and to validate its role as a 
      therapeutic target for CaP therapy. CD44v6 was knocked down in PC-3M CaP cell 
      line using short hairpin RNA. Subcutaneous (s.c.) and orthotopic CaP mouse 
      xenografts were established. The effect of CD44v6 knockdown (KD) on tumour growth 
      was evaluated in both s.c. and orthotopic models. Chemo-/radiotherapy response 
      was evaluated in the s.c. model. Association of CD44v6 with PI3K/Akt pathway was 
      validated using immunohistochemistry staining. We found that KD of CD44v6 
      significantly reduced tumour growth in both models, and enhanced the sensitivity 
      of tumours to chemotherapy and radiotherapy in the s.c. model. In addition, we 
      demonstrated that KD of CD44v6 is associated with downregulation of the 
      PI3K/Akt/mTOR pathway. Our data confirm that CaP growth and 
      chemo-/radiosensitivity in vivo is associated with CD44v6, which holds great 
      promises as a therapeutic target in the treatment of CaP.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Ni, Jie
AU  - Ni J
AD  - Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; St George 
      and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, 
      Australia.
FAU - Cheung, Belamy B
AU  - Cheung BB
AD  - Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Sydney, 
      NSW, 2052, Australia; School of Women's & Children's Health, Faculty of Medicine, 
      UNSW, Sydney, NSW, 2052, Australia.
FAU - Beretov, Julia
AU  - Beretov J
AD  - Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; St George 
      and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, 
      Australia; Anatomical Pathology, NSW Health Pathology, St George Hospital, 
      Kogarah, NSW, 2217, Australia.
FAU - Duan, Wei
AU  - Duan W
AD  - School of Medicine and Centre for Molecular and Medical Research, Deakin 
      University, Waurn Ponds, VIC, 3216, Australia.
FAU - Bucci, Joseph
AU  - Bucci J
AD  - Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; St George 
      and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, 
      Australia.
FAU - Malouf, David
AU  - Malouf D
AD  - Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; Department 
      of Urology, St George Hospital, Kogarah, NSW, 2217, Australia.
FAU - Graham, Peter
AU  - Graham P
AD  - Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; St George 
      and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, 
      Australia.
FAU - Li, Yong
AU  - Li Y
AD  - Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia; St George 
      and Sutherland Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, 2052, 
      Australia; School of Basic Medical Sciences, Zhengzhou University, Henan, 450001, 
      China. Electronic address: y.li@unsw.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CD44v6 antigen)
RN  - 0 (Hyaluronan Receptors)
RN  - 15H5577CQD (Docetaxel)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Chemoradiotherapy/*methods
MH  - Docetaxel/*pharmacology
MH  - Gamma Rays
MH  - *Genetic Variation
MH  - Humans
MH  - Hyaluronan Receptors/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Prostatic Neoplasms/genetics/*pathology/therapy
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Radiation Tolerance/*genetics
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - CD44v6
OT  - Chemotherapy
OT  - PI3K/Akt/mTOR
OT  - Prostate cancer
OT  - Radiotherapy
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/01/20 06:00
MHDA- 2020/11/11 06:00
CRDT- 2020/01/20 06:00
PHST- 2019/10/04 00:00 [received]
PHST- 2020/01/08 00:00 [revised]
PHST- 2020/01/13 00:00 [accepted]
PHST- 2020/01/20 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/01/20 06:00 [entrez]
AID - S0014-4827(20)30044-6 [pii]
AID - 10.1016/j.yexcr.2020.111850 [doi]
PST - ppublish
SO  - Exp Cell Res. 2020 Mar 15;388(2):111850. doi: 10.1016/j.yexcr.2020.111850. Epub 
      2020 Jan 16.