Si Andrew I C, Huang Lin, Xu Jiake, Kumta Shekhar-M, Wood David, Zheng Ming H
Department of Orthopaedic Surgery, University of Western Australia, Nedlands, WA. [corrected].
J Cell Biochem. 2003 Aug 15;89(6):1154-63. doi: 10.1002/jcb.10578.
Matrix metalloproteinases (MMPs) are regarded as a significant regulator in tumor invasion and metastasis. Previous studies have shown that extracellular matrix metalloproteinase inducer (EMMPRIN) in tumor cells induces the synthesis of MMPs. EMMPRIN is abundantly present on the surface of tumor cells and stimulate adjacent stromal cells to synthesize MMPs to induce tumor progression. Giant cell tumor (GCT) of bone is a benign but locally aggressive primary neoplasm of bone. The spindle-shaped mononuclear stromal cells are considered to be the tumor components of GCT, which are capable of inducing osteoclast formation by recruiting the circulating monocyte and macrophage. In this study, we proposed that EMMPRIN is associated with the biological progression and aggressiveness of GCT. We have conducted semi-quantitative RT-PCR to determine the correlation of EMMPRIN expression with the clinical stage of GCT. We have also examined the cellular localization of EMMPRIN in GCT using in-situ hybridization (ISH) and Immunohistochemistry (IH). The results showed that EMMPRIN was present in GCT and its mRNA levels were associated with the clinical stage of GCT. Higher expression level of EMMPRIN was observed in GCT with advanced stage (stage III). There was a great significance (P < 0.05) of EMMPRIN expression between stage I & II and stage III GCTs. Both ISH and IH demonstrated that EMMPRIN is present at the multinuclear osteoclast-like giant cells of GCT, with strong immunostaining on the cell membrane. The stromal-like tumor cells were also positively stained but the intensity was weaker. Interestingly, the production of EMMPRIN in osteoclast-like cells of GCT seems to be regulated by stromal-like tumor cells. Receptor activator of NF-kappaB ligand (RANKL), which has been previously shown to be produced by the stromal-like tumor cells for the recruitment of osteoclast-like giant cells in GCT, enhanced the expression of EMMPRIN mRNA during the differentiation of macrophage-like RAW(264.7) cells into osteoclasts. In short, our studies suggest that EMMPRIN may be an important regulatory factor involved in the biological behaviors of GCT.
基质金属蛋白酶（MMPs）被认为是肿瘤侵袭和转移的重要调节因子。先前的研究表明，肿瘤细胞中的细胞外基质金属蛋白酶诱导剂（EMMPRIN）可诱导MMPs的合成。EMMPRIN大量存在于肿瘤细胞表面，并刺激相邻的基质细胞合成MMPs以诱导肿瘤进展。骨巨细胞瘤（GCT）是一种良性但具有局部侵袭性的原发性骨肿瘤。梭形单核基质细胞被认为是GCT的肿瘤成分，其能够通过募集循环中的单核细胞和巨噬细胞诱导破骨细胞形成。在本研究中，我们提出EMMPRIN与GCT的生物学进展和侵袭性相关。我们进行了半定量逆转录聚合酶链反应（RT-PCR）以确定EMMPRIN表达与GCT临床分期的相关性。我们还使用原位杂交（ISH）和免疫组织化学（IH）检测了EMMPRIN在GCT中的细胞定位。结果显示，EMMPRIN存在于GCT中，其mRNA水平与GCT的临床分期相关。在晚期（III期）GCT中观察到EMMPRIN的表达水平较高。I期和II期GCT与III期GCT之间EMMPRIN表达存在显著差异（P < 0.05）。ISH和IH均表明，EMMPRIN存在于GCT的多核破骨细胞样巨细胞中，细胞膜上有强免疫染色。基质样肿瘤细胞也呈阳性染色，但强度较弱。有趣的是，GCT破骨细胞样细胞中EMMPRIN的产生似乎受基质样肿瘤细胞调节。核因子κB受体活化因子配体（RANKL）先前已被证明由基质样肿瘤细胞产生，用于在GCT中募集破骨细胞样巨细胞，在巨噬细胞样RAW(264.7)细胞分化为破骨细胞的过程中增强了EMMPRIN mRNA的表达。简而言之，我们的研究表明，EMMPRIN可能是参与GCT生物学行为的重要调节因子。
