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CD44 variant 6 is associated with prostate cancer growth and chemo-/radiotherapy response in vivo

Version 2 2024-06-03, 13:50
Version 1 2020-01-30, 14:58
journal contribution
posted on 2024-06-03, 13:50 authored by J Ni, BB 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.

History

Journal

Experimental Cell Research

Volume

388

Article number

ARTN 111850

Pagination

1 - 7

Location

United States

ISSN

0014-4827

eISSN

1090-2422

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

2

Publisher

ELSEVIER INC