犬前列腺癌细胞系（LuMa）伴成骨骨转移。
Canine prostatic cancer cell line (LuMa) with osteoblastic bone metastasis.
机构信息
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
Department of Pathology, Faculty of Veterinary Medicine, Benha University, Benha, Egypt.
出版信息
Prostate. 2020 Jun;80(9):698-714. doi: 10.1002/pros.23983. Epub 2020 Apr 29.
BACKGROUND
Osteoblastic bone metastasis represents the most common complication in men with prostate cancer (PCa). During progression and bone metastasis, PCa cells acquire properties similar to bone cells in a phenomenon called osteomimicry, which promotes their ability to metastasize, proliferate, and survive in the bone microenvironment. The mechanism of osteomimicry resulting in osteoblastic bone metastasis is unclear.
METHODS
We developed and characterized a novel canine prostatic cancer cell line (LuMa) that will be useful to investigate the relationship between osteoblastic bone metastasis and osteomimicry in PCa. The LuMa cell line was established from a primary prostate carcinoma of a 13-year old mixed breed castrated male dog. Cell proliferation and gene expression of LuMa were measured and compared to three other canine prostatic cancer cell lines (Probasco, Ace-1, and Leo) in vitro. The effect of LuMa cells on calvaria and murine preosteoblastic (MC3T3-E1) cells was measured by quantitative reverse-transcription polymerase chain reaction and alkaline phosphatase assay. LuMa cells were transduced with luciferase for monitoring in vivo tumor growth and metastasis using different inoculation routes (subcutaneous, intratibial [IT], and intracardiac [IC]). Xenograft tumors and metastases were evaluated using radiography and histopathology.
RESULTS
After left ventricular injection, LuMa cells metastasized to bone, brain, and adrenal glands. IT injections induced tumors with intramedullary new bone formation. LuMa cells had the highest messenger RNA levels of osteomimicry genes (RUNX2, RANKL, and Osteopontin [OPN]), CD44, E-cadherin, and MYOF compared to Ace-1, Probasco, and Leo cells. LuMa cells induced growth in calvaria defects and modulated gene expression in MC3T3-E1 cells.
CONCLUSIONS
LuMa is a novel canine PCa cell line with osteomimicry and stemness properties. LuMa cells induced osteoblastic bone formation in vitro and in vivo. LuMa PCa cells will serve as an excellent model for studying the mechanisms of osteomimicry and osteoblastic bone and brain metastasis in prostate cancer.
背景
成骨性骨转移是前列腺癌（PCa）患者最常见的并发症。在进展和骨转移过程中，PCa 细胞获得类似于成骨细胞的特性，这种现象称为成骨性模拟，促进了它们在骨微环境中转移、增殖和存活的能力。导致成骨性骨转移的成骨性模拟机制尚不清楚。
方法
我们开发并鉴定了一种新型犬前列腺癌细胞系（LuMa），该细胞系将有助于研究 PCa 中成骨性骨转移和成骨性模拟之间的关系。LuMa 细胞系是从一只 13 岁的杂种去势雄性狗的原发性前列腺癌中建立的。体外测量 LuMa 细胞的增殖和基因表达，并与其他三种犬前列腺癌细胞系（Probasco、Ace-1 和 Leo）进行比较。通过定量逆转录聚合酶链反应和碱性磷酸酶测定测量 LuMa 细胞对颅骨和鼠前成骨细胞（MC3T3-E1）的影响。用荧光素酶转染 LuMa 细胞，通过不同的接种途径（皮下、胫骨内[IT]和心内[IC]）监测体内肿瘤生长和转移。使用放射学和组织病理学评估异种移植物肿瘤和转移。
结果
左心室注射后，LuMa 细胞转移到骨骼、大脑和肾上腺。IT 注射诱导骨髓内新骨形成的肿瘤。与 Ace-1、Probasco 和 Leo 细胞相比，LuMa 细胞的成骨性模拟基因（RUNX2、RANKL 和骨桥蛋白[OPN]）、CD44、E-钙黏蛋白和 MYOF 的信使 RNA 水平最高。LuMa 细胞诱导颅骨缺损生长，并调节 MC3T3-E1 细胞的基因表达。
结论
LuMa 是一种具有成骨性模拟和干性特性的新型犬前列腺癌细胞系。LuMa 细胞在体外和体内诱导成骨性骨形成。LuMa PCa 细胞将成为研究前列腺癌中成骨性模拟和成骨性骨及脑转移机制的优秀模型。
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