Expression of Bone Morphogenetic Protein and its Receptors in Osteosarcoma and Malignant Fibrous Histiocytoma

Mehdi, R; Shimizu, Takuya; Yoshimura, Yasuo; Gomyo, Hiroki; Takaoka, Kunio

doi:10.1093/jjco/hyd073

Cited by 17 publications

(11 citation statements)

References 17 publications

(14 reference statements)

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“…15 Further Prognostic value of BMPs in osteosarcomainvestigations are needed to establish whether BMP-6 is expressed in cartilage tumours. In an earlier study, 17 the expression of BMP2/4 was examined in two specimens of chondroblastic osteosarcoma, but no detectable staining was found. The divergence between these findings and ours might result from the small number of tumours examined in the earlier study and the use of different BMP subtypes…”

Section: Discussionmentioning

confidence: 95%

The expression of bone morphogenetic proteins in osteosarcoma and its relevance as a prognostic parameter

Sulzbacher¹,

Birner²,

Trieb³

et al. 2002

Journal of Clinical Pathology

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Results: The expression of BMP subtypes varied considerably: 28 of the 47 tumours expressed BMP-2/4, 24 expressed BMP-3, 41 expressed BMP-5, 31 expressed BMP-6, 43 expressed BMP-7, and 42 expressed BMP-8. High expression of BMP-6 was found in those parts of the osteosarcoma with a chondroid differentiation (p = 0.016, Mann-Whitney test). No correlation was observed between the response to chemotherapy and the expression of BMPs (p > 0.05, Mann-Whitney test). Univariate analysis showed no correlation between overall survival or progression free survival and the expression of BMPs (p > 0.05, log rank test). Conclusions: BMP-7 and BMP-8 are highly expressed in osteosarcoma. Moreover, high expression of BMP-6 correlates with a chondroid differentiation. In contrast to conclusions derived from previous studies in which small numbers of tumours were investigated, these results indicate that the expression of BMPs does not help to predict the outcome of patients.

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Section: Discussionmentioning

confidence: 95%

The expression of bone morphogenetic proteins in osteosarcoma and its relevance as a prognostic parameter

Sulzbacher¹,

Birner²,

Trieb³

et al. 2002

Journal of Clinical Pathology

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“…However, immunoreactivity in BMPRs is absent in MFH cases. The presence of BMPs and absence of BMPRs can be used to differentiate MFH and fibroblastic type of osteosarcoma [44]. Therefore, the presence of BMP2 and -4 with the absence of BMPRs may be a key to why MFH tumors cells do not ossify or it may be a another layer of complexity to cancer heterogeneity or behavior of BMPs.…”

Section: Evidence Of Bmp Involvement In Tumorigenesismentioning

confidence: 99%

The Yin and Yang of bone morphogenetic proteins in cancer

Singh

Morris

2010

Cytokine & Growth Factor Reviews

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Bone morphogenetic proteins (BMPs) were first studied as growth factors or morphogens of the transforming growth factor-beta super family. These growth molecules, originally associated with bone and cartilage development, are now known to play important roles in morphogenesis and homeostasis in many other tissues. More recently, significant contributions of BMPs, their receptors, and interacting molecules have been linked to carcinogenesis and tumor progression. On the other hand, BMPs can sometimes play a role as a tumor suppressor. Our report highlights these new roles in the pathogenesis of cancer that may suggest novel targets for therapeutic intervention. KeywordsBone Morphogenetic Proteins; Bone morphogenetic receptors; TGF-β; Cancer; Metastasis 1.0. Introduction BMP introduction, signaling cascades, and interacting moleculesBone Morphogenetic Proteins (BMPs) are a family of evolutionarily conserved growth factors and morphogens most of which belong to the transforming growth factor-β (TGF-β) super-family. BMPs were discovered by Marshall Urist in 1965, who found that decalcified bone matrix fragments have bone induction activity when transplanted into rats and rabbits [1]. Wozney et al., (1988) isolated and identified molecules from bone extracts capable of inducing bone and cartilage formation and named them BMPs [2]. Further studies reveal that BMPs not only regulate bone and cartilage, but exert a wide range of morphogenetic activity that is both tissue and context dependent [3,4,5].BMPs exist as dimeric pro-protein complexes in the cytoplasm that are cleaved by proteases before their intended action. After the BMP molecules are secreted, they are further processed by another layer of regulators, Noggin and Chordin, and then bind to their specific receptors on the plasma membrane of their target cells [6,7]. BMPs exert their activities by way of serine-threonine kinase receptors of which there are three type-I and three type-II [8]. Different BMPs show preference in the combination of receptors, but in general utilize one receptor of each type [9,10]. As most BMPs are TGF-β family members, they tend to use the same signaling pathways, principally MAPK and SMAD, although Notch and WNT are also used [11][12][13]. Binding of the BMPs to their specific receptors triggers cross phosphorylation of the type-I receptor by the type-II receptor [14]. The type-I receptor then © 2010 Elsevier Ltd. All rights reserved * Corresponding author at: Stem Cells and Cancer 801 16 th Ave NE Hormel Institute/Univ. Minnesota Austin, MN 55912, USA Phone: 507-437-9630 FAX: 507-437-9606 rmorris@hi.umn.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affec...

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“…It has been recently suggested BMP expression in OS correlates positively with the incidence of metastatic disease and negatively with disease-free survival, although the BMP expression of metastatic OS cells has not been characterized. 1,21,27,33,34 In addition to BMPs, vascular endothelial growth factor (VEGF), a potent neoangiogenic agent widely investigated in oncology, has been implicated in the occurrence of metastasis, 8,11,16,25,28 and high concentrations of VEGF in the sera of patients with OS have been linked to the development of pulmonary metastasis. 15 Noggin is an antagonist of BMP types 2, 4, and 7.…”

mentioning

confidence: 99%

VEGF and BMP Expression in Mouse Osteosarcoma Cells

Weiß

Cooper

Jadlowiec

et al. 2006

Clinical Orthopaedics and Related Research

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Osteosarcoma is the most common primary bone malignancy. Despite improvements in therapy, approximately 30% of patients experience pulmonary metastasis. Expression of several growth factors, including VEGF and BMPs, has been implicated in tumor progression and metastatic potential. We hypothesized increased metastatic potential of mouse osteosarcoma cells positively correlates with the expression of VEGF and BMPs. We studied the expression patterns of these growth factors in two murine osteosarcoma cell lines with varying degrees of metastatic potential: K7M2 (highly metastatic) and K12 (minimally metastatic). Expression of VEGF and BMP2 were higher in the metastatic K7M2 cell line. We also investigated the effects of the BMP antagonist noggin on osteosarcoma growth characteristics in vitro. We noted decreased motility, altered morphology, and increased cell death in the highly metastatic K7M2 cell line. Less metastatic K12 cells showed substantial cell death without clear alteration of motility or morphology. These data suggest BMP2 expression may be an important factor in osteosarcoma metastasis and noggin administration theoretically could block its actions. Inhibition of BMPs and VEGF should be investigated further as a possible strategy for decreasing the incidence of pulmonary metastases in osteosarcoma.

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Expression of Bone Morphogenetic Protein and its Receptors in Osteosarcoma and Malignant Fibrous Histiocytoma

Cited by 17 publications

References 17 publications

The expression of bone morphogenetic proteins in osteosarcoma and its relevance as a prognostic parameter

The expression of bone morphogenetic proteins in osteosarcoma and its relevance as a prognostic parameter

The Yin and Yang of bone morphogenetic proteins in cancer

VEGF and BMP Expression in Mouse Osteosarcoma Cells

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