Expression of parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor in osteoclast-like giant cells
Expression of parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor in osteoclast-like giant cells
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DOI：
10.1078/0344-0338-00359
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Sekine, I
中科院分区：
文献类型：
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作者：
Nakashima, M;Nakayama, T;Sekine, I
破骨细胞样巨细胞（OCGC）在形态学和免疫组化水平上与破骨细胞相似，在肿瘤组织中发育。在骨髓中，甲状旁腺激素（PTH）相关肽（PTHrP）可通过PTH/PTHrP受体（PPR）刺激破骨细胞祖细胞诱导破骨细胞分化。为了评估PTHrP在肿瘤中OCGC形成中的可能参与，我们通过免疫组化分析了PTHrP和PPR在骨巨细胞瘤（GCTB）和含有OCGC的甲状腺未分化癌（ATC）中的表达。在GCTB（n = 5）或ATC（n = 4）的所有病例中，PTHrP在OCGC中被发现强染色，但仅在单个核细胞中微弱染色。PPR在3例GCTB和2例ATC中也有表达。PPR和增殖细胞核抗原（PCNA）的双重染色显示，PPR主要表达于PCNA阴性的单个核细胞和OCGC。这表明OCGC可能来源于非增殖单核细胞通过PTHrP刺激通过PPR。此外，将OCGC中PTHrP和PPR的表达谱与恶性肿瘤中发现的肿瘤性GC（n = 6）、骨关节炎骨中的破骨细胞（n = 5）、反应性GC（包括Langhans型和肺结核异物型）（n = 8）和破裂的表皮囊肿（n = 14）中的PTHrP和PPR表达谱进行比较，以阐明其分布模式是否为OCGC所独有。在所有的恶性肿瘤的情况下，PTHrP和PPR的表达，观察无处不在的肿瘤GC和单核细胞，无论PCNA免疫反应。与此相反，在破骨细胞和反应性胃癌，PTHrP免疫反应中看到在所有的情况下，在22例中的7例，分别，但没有观察到PPR表达。原位杂交证实PTHrP在OCGC和肿瘤性GC中在转录水平表达，但在破骨细胞中不表达。因此，虽然PTHrP的表达是常见的各种类型的多核巨细胞，其免疫组化PPR的配置文件是不同的。我们的结论是，PPR可能在GCTB和ATC的OCGC形成过程中发挥作用。
Osteoclast-like giant cells (OCGC), which resemble osteoclasts at both the morphologic and immunohistochemical levels, develop in neoplastic tissue. In bone marrow, parathyroid hormone (PTH)-related peptide (PTHrP) can induce osteoclast differentiation by stimulating osteoclast progenitors through the PTH/PTHrP receptor (PPR). To evaluate the possible involvement of PTHrP in OCGC formation in tumors, we analyzed both PTHrP and PPR expression by immunohistochemistry in giant cell tumor of bone (GCTB) and anaplastic thyroid cancer (ATC) containing OCGC. In all cases of either GCTB (n = 5) or ATC (n = 4), intense staining for PTHrP was found in OCGC, but only faintly in mononuclear cells. PPR expression in OCGC was also demonstrated in 3 cases of GCTB and 2 cases of ATC. Double staining for PPR and proliferating cell nuclear antigen (PCNA) revealed that PPR was mainly expressed by PCNA-negative mononuclear cells and OCGC in these tumors. This suggests that OCGC might be derived from non-proliferating mononuclear cells by PTHrP stimulation via PPR. Furthermore, the profiles of PTHrP and PPR expression in OCGC were compared with those in the neoplastic GC found in malignancy (n = 6), osteoclasts in bone with osteoarthritis (n = 5), reactive GC, including Langhans-type and foreign body-type in pulmonary tuberculosis (n = 8), and ruptured epidermal cyst (n = 14) in order to clarify whether their distribution pattern was unique to OCGC. In all cases of malignancy, expression of both PTHrP and PPR was observed ubiquitously in neoplastic GC and mononuclear cells regardless of PCNA immunoreactivity. In contrast, in osteoclasts and reactive GC, PTHrP immunoreactivity was seen in all cases and in 7 of 22 cases, respectively, but no PPR expression was observed in either. In situ hybridization confirmed PTHrP expression at the transcriptional level in OCGC and neoplastic GC, but not in osteoclasts. Thus, although PTHrP expression was commonly observed in various types of multinucleated giant cells, their immunohistochemical profiles for PPR were distinct. We conclude that PPR might play a role during OCGC formation in GCTB and ATC.