Barger Anne M, Fan Timothy M, de Lorimier Louis-Philippe, Sprandel Ian T, O'Dell-Anderson Kristen
Department of Pathobiology, University of Illinois at Urbana-Champaign, USA.
J Vet Intern Med. 2007 Jan-Feb;21(1):133-40. doi: 10.1892/0891-6640(2007)21[133:eoraon]2.0.co;2.
Receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis.
Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology.
Forty-two dogs and 6 cats with spontaneously-occurring tumors involving bones or soft tissues were evaluated.
A polyclonal anti-human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor-bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology.
Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x-ray absorptiometry.
In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism.
核因子κB受体激活剂（RANK）、RANK配体（RANKL）和可溶性诱饵受体骨保护素（OPG）构成调节破骨细胞生成的关键轴。在健康状态下，表达RANKL的骨基质细胞和成骨细胞通过RANK连接激活破骨细胞，导致骨吸收的稳态。犬猫的骨骼肿瘤，无论是原发性还是转移性，都可能表达RANKL并直接诱导恶性骨溶解。
犬猫的骨恶性肿瘤可能表达RANKL，从而导致病理性骨吸收和疼痛。此外，骨肿瘤中RANKL的相对表达可能与骨病理的影像学特征相关。
对42只犬和6只猫进行了评估，这些动物患有自发发生的涉及骨骼或软组织的肿瘤。
通过流式细胞术和免疫细胞化学验证了一种多克隆抗人RANKL抗体可用于犬猫细胞。从48只患有肿瘤的动物的骨和软组织肿瘤中收集了50份细胞学标本，并评估了RANKL的表达。在15份犬骨肉瘤（OSA）样本中，RANKL的相对表达与骨病理的影像学特征相关。
在32/44份犬肿瘤样本和5/6份猫肿瘤样本中鉴定出肿瘤细胞表达RANKL。在15只患有OSA的犬中，RANKL的相对表达与通过双能X线吸收法评估的影像学骨溶解或骨矿物质密度均无相关性。
在犬猫中，经典的涉及骨骼并引起疼痛的肿瘤通常可能表达RANKL。确认肿瘤中RANKL的表达是朝着通过RANKL拮抗作用合理应用针对恶性骨溶解的新疗法迈出的必要一步。
