The online version of this article (https://doi.org/10.1186/s13046-018-0884-2) contains supplementary material, which is available to authorized users.
Ruizhe Zhao, Xiaoyu Bei and Boyu Yang contributed equally to this work.
Prostate cancer is one of the most common malignancies. Increasing evidence suggested that endothelial cells may contribute to prostate cancer progression and metastasis. Most recently, autophagy has been proposed to plays a significant role in tumorigenesis and metastasis. Also, it is reported that downregulation of androgen receptor (AR) induces autophagy in prostate cancer cells. However, the underlying mechanisms remain unclear. Here, we aim to explore the role and mechanisms of endothelial cell in prostate cancer progression.
The coculture system was established to test the effect of endothelial cells on prostate cancer cells. We performed antibody array and ELISA were used to profile the cytokine expression pattern of endothelial cells in supernatant. Western blot and RT-PCR were used to determine the mechanism by endothelial cells to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic xenograft mouse models and drug treatment study were conducted to determine the role of endothelial cells in promoting metastatic potential in vivo.
We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo.
Together, our data establish the function for endothelial cells in tumor metastasis and propose new drug target for mCRPC.
Additional file 1: Table S1. (XLSX 10 kb)13046_2018_884_MOESM1_ESM.xlsx
Additional file 2: Figure S1. Cell viability assay for effect of coculturing with HUVEC. (TIF 210 kb)13046_2018_884_MOESM2_ESM.tif
Additional file 3: Figure S2. A. qPCR validation of CCL5 in prostate cancer cells or HUVEC after transfecting siCCL5 for 72 h; B. CCL5 concentration in coculture media tested by ELISA. (TIF 246 kb)13046_2018_884_MOESM3_ESM.tif
Additional file 4: Figure S3. A. Western blotting of PC-3 and PC-3-AR cells and quantification of LC3II/LC3I ratio; B. Cell viability assay for effect of CQ treatment. (TIF 716 kb)13046_2018_884_MOESM4_ESM.tif
Additional file 5: Figure S4. Effect of CCL5 treatment on autophagy by western blotting. (TIF 214 kb)13046_2018_884_MOESM5_ESM.tif
Additional file 6: Figure S5. A. Western blotting of xenograft tumors; B. HE staining of mice organs; C. Mice weight variance. (TIF 3137 kb)13046_2018_884_MOESM6_ESM.tif
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- Endothelial cells promote metastasis of prostate cancer by enhancing autophagy
- BioMed Central
Journal of Experimental & Clinical Cancer Research
Elektronische ISSN: 1756-9966
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