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CD44 variant 6 is associated with prostate cancer growth and chemo-/radiotherapy response in vivo
journal contribution
posted on 2020-03-15, 00:00 authored by J Ni, B B Cheung, J Beretov, Wei DuanWei Duan, J Bucci, D Malouf, P Graham, Y Li© 2020 Elsevier Inc. 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.
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Journal
Experimental Cell ResearchVolume
388Issue
2Article number
111850Pagination
1 - 7Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0014-4827eISSN
1090-2422Publication classification
C1 Refereed article in a scholarly journalUsage metrics
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