Recognition of Invasive Prostate Cancer Using a GHRL Polypeptide Probe Targeting GHSR in a Mouse Model In Vivo

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Author(s): Huamao Ye, Yue Yang, Rui Chen, Xiaolei Shi, Yu Fang, Jun Yang, Yuanzhen Dong, Lili Chen, Jianghua Xia, Chao Wang, Chenghua Yang, Jun Feng, Yang Wang, Chen Lü*, Xiang Feng.

Journal Name: Current Pharmaceutical Design


Background: Ghrelin (GHRL) is a polypeptide, which can specifically bind to the GHSR. The expression of GHSR has significant differences in human normal and prostate cancer tissues. It is meaningful to find an effective diagnostic method for the diagnosis and prognosis of invasive/neuroendocrine prostate cancer.

Methods: GHRL and GHSR mRNAs level were determined by quantitative real-time polymerase chain reaction in PC tissues. The expression of GHRL and GHSR proteins were assessed respectively by western blot and immunohistochemistry. GHRL polypeptide probe was synthesized through standard solid-phase synthesis of polypeptide, and labeled with Alexa Fluor 660. Confocal microscope was used to capture fluorescence images. Living imaging analysis show tumor areas of different invasiveness in mice models.

Results: The level of GHRL and GHSR copy number amplification and mRNA expression were increased in invasive/neuroendocrine prostate cancer, and the protein expression of GHRL and GHSR were similarly boosting in NEPC. The GHRL polypeptide probe could effectively bind to GHSR. In PC3, we found that GHRL probe specifically bind to GHSR on cell membrane and accumulated in cells through internalization after binding. Living imaging in mice models showed that there were different signal intensities in tumor areas of different invasiveness.

Conclusion: The GHSR and GHRL might be used to the molecular imaging diagnosis for invasive/neuroendocrine prostate cancer in future.

Keywords: Prostate cancer, invasive/neuroendocrine prostate cancer, GHRL, GHSR, polypeptide probe

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1381612826666191227160001
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