Prostate cancer promotes a vicious cycle of bone metastasis progression through inducing osteocytes to secrete GDF15 that stimulates prostate cancer growth and invasion
| Autor: | Evan T. Keller, Yi Lu, Jian Zhang, Wenchu Wang, Xin Yang, Jinlu Dai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Growth Differentiation Factor 15 Cell Bone Neoplasms Mice SCID Biology urologic and male genital diseases Osteocytes Article Metastasis Cell Line 03 medical and health sciences Prostate cancer Mice 0302 clinical medicine Cell Movement Mice Inbred NOD Cell Line Tumor Genetics medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis Molecular Biology Cell Proliferation Gene knockdown Cell growth Bone metastasis Prostatic Neoplasms medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Osteocyte Cancer cell Cancer research Disease Progression Signal Transduction |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | Bone is the most frequent site of prostate cancer (PCa) metastasis; however, little is known about the role of the most common cell in bone, the osteocyte (OCy), in cancer biology. In this study we explored the crosstalk between PCa cells and OCys to determine if it contributes to PCa progression. PCa cells induced OCys to promote PCa proliferation, migration and invasion. A chemokine screen revealed that PCa cell induced OCys to produce growth-derived factor 15 (GDF15). Knockdown of GDF15 in OCys demonstrated that PCa cells conferred the ability on OCys to promote PCa proliferation, migration and invasion through GDF15. Consistent with this finding was the observation that the GDF15 receptor, GFRAL, was expressed on multiple PCa cell lines. Transcription factor array screening of PCa cells exposed to OCys with or without knockdown of GDF15 revealed that GDF15 in OCys promoted early growth response 1 (EGR1) expression in the PCa cells. Knockdown of EGR1 expression in PCa cells revealed it was required for the OCy-derived GDF15-mediated induction of in vitro PCa cell proliferation, migration and invasion. Subcutaneous co-injection of PCa cells and OCys into mice revealed that OCys promoted tumor growth in vivo, which was diminished by knockdown of GDF15 in the OCys. Knockdown of GDF15 in the tibiae diminished growth of PCa cancer cells injected into the tibiae, which was accompanied by decreased tumor cell proliferation and EGR1 expression. These results shed light on a novel mechanism through which PCa cells educate OCys to promote progression of PCa bone metastasis. They also suggest that targeting of GDF15-based and EGR1-based signaling pathways should be further explored for their potential to diminish progression of PCa bone metastasis. |
| Databáze: | OpenAIRE |
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