Upregulation of CRMP4, a new prostate cancer metastasis suppressor gene, inhibits tumor growth in a nude mouse intratibial injection model

Zhou,Wei; Xie,Peigen; Pang,Mao; Yang,Bu; Fang,Youqiang; Shu,Tao; Liu,Chang; Wang,Xuan; Zhang,Liangming; Li,Shangfu; Rong,Limin

doi:10.3892/ijo.2014.2705

Upregulation of CRMP4, a new prostate cancer metastasis suppressor gene, inhibits tumor growth in a nude mouse intratibial injection model

Authors:
- Wei Zhou
- Peigen Xie
- Mao Pang
- Bu Yang
- Youqiang Fang
- Tao Shu
- Chang Liu
- Xuan Wang
- Liangming Zhang
- Shangfu Li
- Limin Rong
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Affiliations: Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China, Department of Urinary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
Published online on: October 10, 2014 https://doi.org/10.3892/ijo.2014.2705
Pages: 290-298

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Abstract

Prostate cancer, the most commonly diagnosed male cancer in North America, has a high incidence of bone metastasis. Our previous study showed collapsin response mediator protein 4 (CRMP4) gene inhibited prostate cancer migration and invasion. In this study, we investigated whether overexpression of CRMP4 gene in prostate cancer cells inhibit tumor bone metastasis. The stable prostate cancer cells overexpressing the CRMP4 gene were constructed using lentivirus infection. Prostate cancer bone metastasis nude mouse model was built though orthotopic prostate implantation, intracardiac injection and intratibial injection with CRMP4 overexpress and control cancer cells. Small animal PET/CT scanning results showed no difference of bone metastatic capacity in orthotopic and intracardiac injection models between CRMP4 overexpression and control group, while CRMP4 overexpression inhibited tumor growth in the intratibial injection model. Moreover, our in vitro study showed CRMP4 overexpression downregulates the Neuropilin1 (NRP1) expression and upregulate the Noggin expression. Immunohistochemical staining of the hind limbs of intratibial injection model was confirmed with cytological experiments. Taken together, our research indicated CRMP4 inhibits prostate cancer cells growth in the nude mouse bone microenvironment and this effect may relate with regulation of NRP1 and Noggin expression.

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