Journal Article

Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo‐osteogenic balance in bone marrow

Zhu, Jiaojiao, Li, Xue, Wang, Cuizhe, Li, Wei, Wang, Jingzhou, Chen, Keru, Qiu, Tongtong, Pang, Huai, Xie, Jianxin, Zhang, Jun, Ma, Yinghua

2020

Overview

Prostate cancer (PCa) continues to be the most common, noncutaneous cancer in men. Bone is the most frequent site of PCa metastases, and up to 90% of patients with advanced PCa develop bone metastases. An altered bone marrow microenvironment, induced by obesity, is a significant mediator for the bone tropism of PCa. However, the specific molecular mechanisms by which obesity causes changes in the bone marrow microenvironment, leading to PCa bone metastasis, are not fully understood. Our results demonstrate that a high‐fat diet (HFD) leads to dyslipidemia and changes in bone marrow of nude mice: an increase in the area and number of adipocytes and a reduction in the area and number of osteoblasts. Moreover, a HFD promoted cyclooxygenase 2 (COX2) expression and inhibited osteoprotegerin (OPG) expression in the bone microenvironment. Additionally, the total level of free fatty acids (FFAs) and caprylic acid (C8:0) was significantly higher in PCa patients with bone metastases. In vitro, caprylic acid (C8:0) promoted bone mesenchymal stem cell (MSC)‐derived adipocytic differentiation, COX2 expression, and prostaglandin E2 (PGE2) secretion, whereas osteoblastic differentiation and OPG expression were reduced. Furthermore, caprylic acid (C8:0)‐treated adipocytes promoted the invasion and migration of PCa cells. Taken together, our findings suggest caprylic acid (C8:0) promotes bone metastasis of PCa by dysregulated adipo‐osteogenic balance of bone marrow. Obesity‐induced high level of free fatty acids could change the bone marrow microenvironment that provides \"fertile soil\" for bone metastasis of prostate cancer. It was found for the first time that increased caprylic acid (C8:0) could promote the area and number of adipocytes and the level of cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) in the bone marrow cavity, which causes prostate cancer bone metastasis.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adipocytes / Adipocytes - drug effects / Adipocytes - metabolism / Adipocytes - pathology / adipo‐osteogenic balance / Animals / Antibodies / Bone and Bones - drug effects / Bone and Bones - metabolism / Bone and Bones - pathology / Bone cancer / Bone marrow / Bone Marrow - drug effects / Bone Marrow - metabolism / Bone Marrow - pathology / bone marrow microenvironment / Bone Neoplasms - metabolism / Bone Neoplasms - pathology / Cancer / Caprylates - pharmacology / caprylic acid (C8:0) / Carcinogenesis / Cell differentiation / Cell Differentiation - drug effects / Cell Line / Cell Line, Tumor / Cell migration / Cyclooxygenase 2 - metabolism / Cyclooxygenase-2 / Dyslipidemia / Ethanol / Fatty acids / High fat diet / Hospitals / Humans / Laboratory animals / Male / Medical ethics / Mesenchymal stem cells / Mesenchyme / Metastases / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Molecular modelling / Obesity / Octanoic acid / Original / Osteoblastogenesis / Osteoblasts / Osteoblasts - drug effects / Osteoblasts - metabolism / Osteoblasts - pathology / Osteoprotegerin / PC-3 Cells / Prostaglandin E2 / Prostate cancer / prostate cancer bone metastasis / Prostatic Neoplasms - metabolism / Prostatic Neoplasms - pathology / Stem cells / Tropism / Tumor Microenvironment - drug effects / Yeast