Expression and localization of extracellular matrix metalloproteinase inducer in giant cell tumor of bone.
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.
Si
Andrew I C
AI
Department of Orthopaedic Surgery, University of Western Australia, Nedlands, WA. [corrected].
Huang
Lin
L
Xu
Jiake
J
Kumta
Shekhar-M
SM
Wood
David
D
Zheng
Ming H
MH
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000166:cytology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology; D053244:Osteoprotegerin; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C497887:Bsg protein, mouse; C079432:Bsg protein, rat; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat; D019716:Tissue Inhibitor of Metalloproteinase-2; D051926:Basigin; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1