Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802-4714, USA.
J Vet Intern Med. 2013 Jul-Aug;27(4):955-63. doi: 10.1111/jvim.12121. Epub 2013 Jun 4.
In dogs with appendicular osteosarcoma (OSA), increased pretreatment serum bone-specific alkaline phosphatase (BALP) activity is a negative prognostic factor, associated with shorter disease-free intervals and survival times, but a biologic basis for observed differential serum BALP activities in canine OSA patients remains incompletely defined.
Serum BALP activity will correlate with absolute tumor burden in dogs with OSA.
This study included 96 client-owned dogs with appendicular OSA.
In canine OSA cell lines, the expression and membranous release of BALP was evaluated in vitro. The correlation between serum BALP activity and radiographic primary tumor size was evaluated in OSA-bearing dogs. In dogs developing visceral OSA metastases, serial changes in serum BALP activities were evaluated in relation to progression of macroscopic metastases, and visceral metastatic OSA cells were evaluated for BALP expression.
In vitro, BALP expression was not associated with either tumorigenic or metastatic phenotype, rather the quantity of membranous BALP released was proportional with cell density. In dogs devoid of macroscopic metastases, there was a positive correlation between serum BALP activity and absolute primary tumor size. In dogs with progressive OSA metastases, serum BALP activity increased and coincided with the development of macroscopic metastases. OSA cells derived from visceral metastatic lesions retained BALP expression.
Tumor burden is a determinant of serum BALP activity in dogs with appendicular OSA. The association between increased pretreatment BALP activity and negative clinical prognosis may simply be attributed to greater initial tumor burden, and consequently more advanced tumor stage.
在患有附肢骨肉瘤(OSA)的犬中,预处理血清骨特异性碱性磷酸酶(BALP)活性升高是一个负面的预后因素,与无病间隔和生存时间较短相关,但犬 OSA 患者观察到的血清 BALP 活性差异的生物学基础仍不完全明确。
血清 BALP 活性与 OSA 犬的肿瘤负荷呈正相关。
本研究纳入了 96 只患有附肢 OSA 的患犬。
在犬 OSA 细胞系中,体外评估 BALP 的表达和膜释放。评估 OSA 犬中血清 BALP 活性与放射影像学原发性肿瘤大小之间的相关性。在发生内脏 OSA 转移的犬中,评估血清 BALP 活性的连续变化与宏观转移进展的关系,并评估内脏转移性 OSA 细胞中 BALP 的表达。
在体外,BALP 的表达与致瘤性或转移性表型均无关,而是膜结合的 BALP 释放量与细胞密度成正比。在没有宏观转移的犬中,血清 BALP 活性与原发性肿瘤的绝对大小呈正相关。在发生 OSA 转移进展的犬中,血清 BALP 活性增加,与宏观转移的发生相吻合。来自内脏转移性病变的 OSA 细胞保留 BALP 表达。
肿瘤负荷是犬附肢 OSA 中血清 BALP 活性的决定因素。术前 BALP 活性升高与临床预后不良之间的关联可能仅仅归因于初始肿瘤负荷更大,进而肿瘤分期更晚。