Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions

Kumta, S. M.; Huang, Lin; Cheng, Y.Y.; Chow, Louis T. C.; Lee, K.M.; Zheng, Minghao

doi:10.1016/s0024-3205(03)00434-x

Cited by 101 publications

(103 citation statements)

References 18 publications

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“…4C, 4D). In agreement with other reports (4,6,8,9,16,29), our in situ hybridization showed more intense signals of VEGF mRNA in the metastatic lesion compared to those on normal osteoblasts or bone marrow stromal cells. VEGF appears to plays a pivotal role in promotion of angiogenesis during the onset of metastases, evidenced by reports in which inhibition of its function effectively prevented tumor growth by hindering complete blood vessel formation (7,15).…”

Section: Discussionsupporting

confidence: 93%

Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line

Shimamura

Amizuka

et al. 2005

Biomed. Res.

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Bone tissue, with its dynamic microenvironment featuring osteoclastic bone resorption, angiogenesis and matrix degradation, appears to facilitate proliferation of tumor cells after the onset of bone metastasis. In this study, we examined metastatic lesions in the femora of BALB/c nu/nu mice two weeks after intracardiac injection with human breast carcinoma MDA-231 cells. Histopathological observations showed the metastatic lesions close to the chondro-osseous junction, and revealed MDA-231 cells loosely intermingled with different cell types such as osteoblasts, fibroblastic stromal cells, osteoclasts and endothelial cells. In the metastatic nest, many tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts accumulated in direct contact with or were close to alkaline phosphatase (ALPase)-or receptor activator of NF-κB ligand (RANKL)-positive osteoblastic cells. It seems likely that osteoclastogenesis is mediated through cell-to-cell contacts with ALPase-and RANKL-expressing osteoblastic cells. Formation of many capillaries lacking complete basal membranes and pericytes ratified the results of in situ hybridization, which revealed intense expression of VEGF in tumor nests, and therefore, indicated ongoing tumor-induced angiogenesis. The tumor cells possessed matrix metallo-proteinases (MMPs)-1 and -9, and frequently extended their stout cytoplasmic processes into fragmented fibrillar components of the growth plate cartilage, implicating degradation of cartilaginous matrix. Thus, osteolytic bone metastasis has demonstrated pathological features as tumor-induced angiogenesis and degradation of extracellular matrix, in addition to osteoclastogenesis. This complex interplay between tumor cells and host tissues may enable and nourish the establishment of a microenvironment that facilitates tumor progression.Bone metastasis is an important clinical entity in patients suffering from some sorts of malignant tumors, and blood circulation comes out as a vector for tumor cells to spread and establish metastatic lesions. Noteworthy is the venous drainage from the breast directly into the vertebral venous plexus, which may explain the high rates of bone metastasis by breast carcinoma cells. Bone microenvironment per se also seems to play an important role, facilitating colonization and proliferation of tumor cells. Breast carcinomas show a trend toward bone metastasis, especially if compared to fewer bone metasta-

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Section: Discussionsupporting

confidence: 93%

Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line

Shimamura

Amizuka

et al. 2005

Biomed. Res.

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“…In addition to IL6, higher levels of the urokinase-type plasminogen activator (u-PA), its receptor (u-PAR) and its inhibitor (PAI-1) have been found in GCT and/or their pulmonary metastases [13]. There may also be links between the expression of matrix metallo-proteinases in GCT and biological behaviour because the expression of MMP-9 can sometimes occur and be maintained by means of an auto-stimulation mechanism in conjunction with interleukin-1ß [23].…”

Section: Additional Pathogenetic Factors In Gctmentioning

confidence: 99%

Giant cell tumour of bone: morphological, biological and histogenetical aspects

Werner

2006

International Orthopaedics (SICOT)

212

156

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The giant cell tumour of bone (GCT) is a locally aggressive intraosseous neoplasm of obscure biological behaviour. Although well defined in clinical, radiological and histological terms, detailed information on its biological development is still relatively incomplete. The tumoral tissue consists of three cell types -the neoplastic giant cell tumour stromal cells (GCTSC), representing the proliferative fraction, secondarily recruited mononuclear histiocytic cells (MNHC) and multinuclear giant cells (MNGC). These cellular components interact together with factors that have a role in regulating osteoclast function in normal bone tissue (e.g. RANK, RANKL, OPG, M-CSF). Recent publications suggest that the neoplastic stromal cells express differentiation features of mesenchymal stem cells. Further research of the pathogenesis of GCT as well as the complex interactions of its cellular populations may provide the knowledge necessary for developing approaches for a biological-based therapy of this neoplasm.Résumé Les tumeurs à cellules géantes (GCT) sont des tumeurs localement agressives de type néoplasme intra osseux don't les mécanismes biologiques restent relativement obscurs. Cependant si ces tumeurs sont bien définies sur le plan clinique, radiologique et histologique, les détails marquants de leur développement biologique restent inconnus. Le tissu tumoral consiste en un stroma de tumeurs à cellules géantes (GCTSC) qui représente la partie prolifér-ative de la tumeur avec adjonction secondaire de cellules de type histogitaire mononuclées (MNHC) et de cellules géantes (MNGC). Ces composants cellulaires interagissent avec un certain nombre de facteurs régulant l'action ostéoclastique du tissu osseux normal (e.g. RANK, RANKL, OPG, M-CSF). De récentes publications permettent de penser que ce stroma cellulaire de type néoplasique exprime une différenciation de cellules mésenchymateuses. De prochaines recherches sur la pathogénèse des tumeurs à cellules géantes ainsi que sur les interactions complexes des différentes populations cellulaires devraient permettre d'approcher un traitement médical pour ce type de néoplasme.

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confidence: 99%

“…Multinucleated giant cells in ABCs express osteolytic features of osteoclasts with high levels of matrix metalloproteinases (MMP-9 and MMP-10), tartarate-resistant acid phosphatase, and cathepsin K [23,26]. ABCs and osteolytic lesions of bone reportedly express high levels of vascular endothelial growth factor (VEGF) in addition to MMPs [23]. In ABCs, the bony destructive process is largely associated with TRE17/USP6 oncogene promotion and upregulation of MMP production, similar to destructive processes associated with MMP production in bone malignancies [5,43].…”

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confidence: 99%

Percutaneous Doxycycline Treatment of Aneurysmal Bone Cysts With Low Recurrence Rate: A Preliminary Report

Shiels

Mayerson

2013

Clinical Orthopaedics &Amp; Related Research

115

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Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions

Cited by 101 publications

References 18 publications

Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line

Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line

Giant cell tumour of bone: morphological, biological and histogenetical aspects

Percutaneous Doxycycline Treatment of Aneurysmal Bone Cysts With Low Recurrence Rate: A Preliminary Report

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