Characterization of bone resorption in novel in vitro and in vivo models of oral squamous cell carcinoma
Characterization of bone resorption in novel in vitro and in vivo models of oral squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2011.12.012
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发表时间：
2012-06-01
期刊：
影响因子：
4.8
通讯作者：
Rosol, Thomas J.
中科院分区：
文献类型：
--
作者：
Martin, Chelsea K.;Dirksen, Wessel P.;Rosol, Thomas J.
口腔鳞状细胞癌（OSCC）是人类和猫中最常见的口腔恶性肿瘤，经常侵犯骨骼。本研究的目的是确定猫骨鳞癌在溶骨行为和骨吸收激动剂的表达方面是否可以作为人类骨鳞癌的相关模型。新的猫OSCC细胞系（SCCF2和SCCF3）来源于自发性癌。研究人员比较了已建立的猫OSCC细胞系（SCCF1）和3个人OSCC细胞系（UMSCC-12、A253和SCC25）的基因表达和溶骨行为。采用体外共培养技术研究OSCC与骨和小鼠前成骨细胞（MC3T3）的相互作用。采用体内生物发光成像、Faxitron x线摄影和显微镜观察裸鼠异种移植物生长和骨侵袭情况。表达最高水平甲状旁腺激素相关蛋白（PTHrP）的人和猫OSCC与体外和体内骨吸收和破骨细胞发生有关。MC3T3细胞在条件培养基中，与微创SCCF3细胞相比，骨侵袭SCCF2细胞的核因子κ B配体受体激活因子（RANKL）表达增加，骨保护素（OPG）表达减少，这被中和性抗pthrp抗体部分逆转。在骨条件培养基中培养的人和猫OSCC细胞PTHrP分泌和增殖增加。猫oscc诱导的骨吸收与肿瘤细胞分泌PTHrP和小鼠成骨前细胞中RANKL:OPG表达比升高有关。骨- cm增加OSCC的增殖和PTHrP的分泌。猫OSCC的临床前模型概括了自发性OSCC的骨侵袭表型特征，将有助于未来临床前和骨侵袭行为的机制研究。(C) 2012 Elsevier Ltd.版权所有。
Oral squamous cell carcinoma (OSCC) is the most commonly diagnosed oral malignancy in humans and cats and frequently invades bone. The objective of this study was to determine if feline OSCC serves as a relevant model of human OSCC in terms of osteolytic behavior and expression of bone resorption agonists. Novel feline OSCC cell lines (SCCF2 and SCCF3) were derived from spontaneous carcinomas. Gene expression and osteolytic behavior were compared to an established feline OSCC cell line (SCCF1) and three human OSCC cell lines (UMSCC-12, A253 and SCC25). Interaction of OSCC with bone and murine pre-osteoblasts (MC3T3) was investigated using in vitro co-culture techniques. In vivo bioluminescent imaging, Faxitron radiography and microscopy were used to measure xenograft growth and bone invasion in nude mice. Human and feline OSCC expressing the highest levels of parathyroid hormone-related protein (PTHrP) were associated with in vitro and in vivo bone resorption and osteoclastogenesis. MC3T3 cells had increased receptor activator of nuclear factor kappa B ligand (RANKL) expression and reduced osteoprotegerin (OPG) expression in conditioned medium from bone-invasive SCCF2 cells compared to minimally bone invasive SCCF3 cells, which was partially reversed with a neutralizing anti-PTHrP antibody. Human and feline OSCC cells cultured in bone-conditioned medium had increased PTHrP secretion and proliferation. Feline OSCC-induced bone resorption was associated with tumor cell secretion of PTHrP and with increased RANKL:OPG expression ratio in mouse preosteoblasts. Bone-CM increased OSCC proliferation and secretion of PTHrP. The preclinical models of feline OSCC recapitulated the bone-invasive phenotype characteristic of spontaneous OSCC and will be useful to future preclinical and mechanistic studies of bone invasive behavior. (C) 2012 Elsevier Ltd. All rights reserved.