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CD44 is a biomarker associated with human prostate cancer radiation sensitivity

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Abstract

CD44 plays an important role in cancer metastasis, chemotherapy, and radiation resistance. The present study investigated the relationship of CD44 expression and radioresistance, and the potential mechanisms of CD44 in radiosensitivity using prostate cancer (CaP) cell lines. CD44 was knocked down in three CaP cell lines (PC-3, PC-3M-luc, and LNCaP) using small interfering RNA (siRNA) and clonogenic survival fractions after single dose irradiation were compared before and after CD44 knocking down (KD). The effect of radiation on cell cycle distribution was examined by flow cytometry and the cell cycle-related protein levels of phospho-Chk1 and phospho-Chk2 were ascertained by Western blotting. The expression of the DNA double strand break (DSB) marker-γH2AX was also quantified by immunofluorescence staining. Our results indicate that the down-regulation of CD44 enhanced radiosensitivity in PC-3, PC-3M-luc, and LNCaP CaP cells, the sensitizing enhancement ratio for these cell lines was 2.3, 1.3, and 1.5, respectively and that the delay of DNA DSB repair in low CD44-expressing KD CaP cells correlated with ineffective cell cycle arrest and the delayed phosphorylation of Chk1 and Chk2. These findings suggest that CD44 may be a valuable biomarker and a predictor of radiosensitivity in CaP treatment.

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Abbreviations

CaP:

Prostate cancer

CD44s:

Standard CD44

CD44v:

CD44 isoforms or variants

CSC:

Cancer stem cell

DPBS:

Dulbecco’s phosphate-buffered saline

DSB:

DNA double strand break

EBRT:

External beam irradiation therapy

ECL:

Enhanced chemiluminescence

ECM:

Extracellular matrix

FACS:

Fluorescence-activated cell sorting

HA:

Hyaluronan

HNSCC:

Head and neck squamous cell carcinoma

HRP:

Horseradish peroxidase

LQ:

Linear quadratic

KD:

Knocking down

PI:

Propidium iodide

SER:

Sensitivity enhancement ratio

siRNA:

Small interfering RNA

SSD:

Source surface distance

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Acknowledgments

We appreciate the technical support from Mr. Ken Hopper, Mr. Ese Enari and Ms. Julia Beretov at the Cancer Care Centre, St George Hospital, Sydney, Australia. This study was supported by a Career Development Fellowship from National Health Medical Research Council (NHMRC) (Yong Li), Australia; St George Hospital Cancer Research Trust Fund (Peter H Graham), Sydney, Australia; and China Scholarship Council (WeiWei Xiao), China.

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Authors and Affiliations

  1. Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia

    WeiWei Xiao, Peter H. Graham, Carl A. Power, Jingli Hao, John H. Kearsley & Yong Li

  2. Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia

    WeiWei Xiao, Peter H. Graham, Jingli Hao, John H. Kearsley & Yong Li

  3. Biological Resources Imaging Laboratory, University of New South Wales, Sydney, NSW, Australia

    Carl A. Power

  4. Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    WeiWei Xiao

  5. State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University, Guangzhou, China

    WeiWei Xiao

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  1. WeiWei Xiao
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Correspondence to Yong Li.

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Xiao, W., Graham, P.H., Power, C.A. et al. CD44 is a biomarker associated with human prostate cancer radiation sensitivity. Clin Exp Metastasis 29, 1–9 (2012). https://doi.org/10.1007/s10585-011-9423-7

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  • DOI: https://doi.org/10.1007/s10585-011-9423-7

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