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CD44 variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance

Version 2 2024-06-06, 05:13
Version 1 2014-11-12, 10:38
journal contribution
posted on 2024-06-06, 05:13 authored by J Ni, PJ Cozzi, JL Hao, J Beretov, L Chang, Wei DuanWei Duan, Sarah ShigdarSarah Shigdar, WJ Delprado, PH Graham, J Bucci, JH Kearsley, Y Li
Prostate cancer (CaP) is the second leading malignancy in older men in Western countries. The role of CD44 variant 6 (CD44v6) in CaP progression and therapeutic resistance is still uncertain. Here, we investigated the roles of CD44v6 in CaP metastasis and chemo/radioresistance. Expression of CD44v6 in metastatic CaP cell lines, human primary CaP tissues and lymph node metastases was assessed using immunofluorescence and immunohistochemistry, respectively.

History

Journal

Prostate

Volume

74

Pagination

602-617

Location

Hoboken, NJ

Publisher DOI

ISSN

0270-4137

eISSN

1097-0045

Language

eng

Author URL

Notes

1097-0045 Ni, Jie Cozzi, Paul J Hao, Jing L Beretov, Julia Chang, Lei Duan, Wei Shigdar, Sarah Delprado, Warick J Graham, Peter H Bucci, Joseph Kearsley, John H Li, Yong Journal Article Research Support, Non-U.S. Gov't United States Prostate. 2014 May;74(6):602-17. doi: 10.1002/pros.22775. Epub 2014 Feb 12. INTRODUCTION: Prostate cancer (CaP) is the second leading malignancy in older men in Western countries. The role of CD44 variant 6 (CD44v6) in CaP progression and therapeutic resistance is still uncertain. Here, we investigated the roles of CD44v6 in CaP metastasis and chemo/radioresistance. Expression of CD44v6 in metastatic CaP cell lines, human primary CaP tissues and lymph node metastases was assessed using immunofluorescence and immunohistochemistry, respectively. METHODS: Knock down (KD) of CD44v6 was performed in PC-3M, DU145, and LNCaP cells using small interfering RNA (siRNA), and confirmed by confocal microscope, Western blot and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The adhesive ability and invasive potential were assessed using a hyaluronic acid (HA) adhesion and a matrigel chamber assay, respectively. Tumorigenesis potential and chemo-/radiosensitivity were measured by a sphere formation assay and a colony assay, respectively. RESULTS: Over-expression of CD44v6 was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of CD44v6 suppressed CaP proliferative, invasive and adhesive abilities, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated epithelial-mesenchymal transition (EMT), PI3K/Akt/mTOR, and Wnt/beta-catenin signaling pathway proteins in vitro. CONCLUSIONS: Our findings demonstrate that CD44v6 is an important cancer stem cell-like marker associated with CaP proliferation, invasion, adhesion, metastasis, chemo-/radioresistance, and the induction of EMT as well as the activation PI3K/Akt/mTOR and Wnt signaling pathways, suggesting that CD44v6 is a novel therapeutic target to sensitize CaP cells to chemo/radiotherapy.

Publication classification

C Journal article, C1 Refereed article in a scholarly journal

Copyright notice

2014, Wiley-Blackwell

Issue

6

Publisher

Wiley-Blackwell

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    Research Publications

    Categories

    Keywords

    CD44 variant 6PI3K/Akt/mTOR pathwayWnt pathwaychemoresistanceprostate cancerradioresistanceAntigens, CD44Cell Line, TumorCell ProliferationHumansLymphatic MetastasisMalePhosphorylationProstatic NeoplasmsProto-Oncogene Proteins c-aktAntigens, CD44/genetics/*metabolism Cell Line, Tumor Cell Proliferation Humans Lymphatic Metastasis/*genetics/pathology Male Phosphorylation Prostatic Neoplasms/genetics/*metabolism/pathology Proto-Oncogene Proteins c-akt/metabolism CD44 variant 6 PI3K/Ak111201 Cancer Cell Biology920102 Cancer and Related DisordersSchool of MedicineMolecular and Medical Research Group

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    All Rights Reserved

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