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

Sulzbacher, Irene; Birner, Peter; Trieb, Klemens; Pichlbauer, Ernest G.; Lang, Susanna

doi:10.1136/jcp.55.5.381

Cited by 68 publications

(56 citation statements)

References 20 publications

(14 reference statements)

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“…Overexpression of BMPs has been described in other cancer types, such as osteosarcoma, 24 breast cancer, 25,26 pancreatic cancer 27 and malignant melanoma. 28 The expression of BMPs has been shown not to confer prognostic value in predicting the outcome of patients with osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

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The prognostic significance of BMP-6 signaling in prostate cancer

et al. 2008

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The importance of bone-morphogenetic proteins in prostate cancer is well recognized. Bone-morphogenetic protein-6 overexpression has been shown to increase the aggressiveness and invasiveness of prostate cancer cells. Recent studies on noggin and sclerostin, potent inhibitors of bone-morphogenetic protein signaling, have found that noggin also modifies the ability of prostate cancer cells to metastasize to bone. Taken together, these results suggest that bone-morphogenetic protein-6 signaling is important in prostate cancer progression. Our study investigated the expression of bone-morphogenetic protein-6, noggin and sclerostin in human prostate specimens (n ¼ 136) by immunohistochemical staining. We found that bone-morphogenetic protein-6 was increased (Po0.001), whereas sclerostin was decreased (P ¼ 0.004) in prostate cancer compared with nodular hyperplasia. In addition, significantly higher level of bone-morphogenetic protein-6 expression was observed in high-grade prostate cancer with Gleason score Z7 (P ¼ 0.027). Bone-morphogenetic protein-6, noggin and sclerostin alone could not predict the development of distant metastasis in our patient cohort. However, high level of bone-morphogenetic protein-6 and low level of noggin, or high level of bonemorphogenetic protein-6 and low level of both noggin and sclerostin expression in primary prostate cancer significantly predicted development of distant metastasis. The predictive value was still valid when only high-grade prostate cancers were included or when patients with secondary lesion other than bone were excluded. Taken together, these results suggest that a high level of bone-morphogenetic protein-6 signaling, resulting from increased expression of bone-morphogenetic protein-6 and decreased expression of its inhibitors, might promote the development of prostate cancer metastases. Our results also imply the potential use of bone-morphogenetic protein-6, noggin and sclerostin expression together as a prognostic predictor for metastatic progression of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

“…28 The expression of BMPs has been shown not to confer prognostic value in predicting the outcome of patients with osteosarcoma. 24 Further studies of BMP activity using a similar approach to ours might make clear the prognostic significance of BMP activity in other cancers.…”

Section: Discussionmentioning

confidence: 99%

The prognostic significance of BMP-6 signaling in prostate cancer

et al. 2008

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“…3,40 Interestingly, BMPs and/or their receptors are readily expressed in OS cells. [51][52][53][54][55][56] Thus, understanding the genetic Disrupted osteogenic differentiation in osteosarcoma X Luo et al and molecular underpinning of the differentiation defects in human OS tumors should allow us to reconstruct the tumorigenic events in osteoprogenitors and to develop rational differentiation therapeutics as an integral part of the clinical management of human OS.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects

Luο

Chen

Song

et al. 2008

Laboratory Investigation

196

307

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Osteosarcoma (OS) is the most common primary malignancy of bone. Here, we investigated a possible role of defective osteoblast differentiation in OS tumorigenesis. We found that basal levels of the early osteogenic marker alkaline phosphatase (ALP) activity were low in OS lines. Osteogenic regulators Runx2 and OSX, and the late marker osteopontin (OPN) expressed at low levels in most OS lines, indicating that most OS cells fail to undergo terminal differentiation. Furthermore, OS cells were refractory to osteogenic BMP-induced increases in ALP activity. Osteogenic BMPs were shown to upregulate early target genes, but not late osteogenic markers OPN and osteocalcin (OC). Furthermore, osteogenic BMPs failed to induce bone formation from human OS cells, rather effectively promoted OS tumor growth in an orthotopic OS model. Exogenous expression of early target genes enhanced BMP-stimulated OS tumor growth, whereas osteogenic BMP-promoted OS tumor growth was inhibited by exogenous Runx2 expression. These results suggest that alterations in osteoprogenitors may disrupt osteogenic differentiation pathway. Thus, identifying potential differentiation defects in OS tumors would allow us to reconstruct the tumorigenic events in osteoprogenitors and to develop rational differentiation therapies for clinical OS management.

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“…Moreover, BMP expression has been found to correlate with metastasis in osteosarcoma [45], while overexpression of BMP-9 reduces invasion and migration properties of osteosarcoma cells [46]. Conversely, analysis of 47 human osteosarcomas found no correlations between BMP expression and prognostic outcomes [47]. Furthermore, BMPs have also been shown to induce bone formation in human osteosarcoma cells [48].…”

Section: Metastasismentioning

confidence: 99%

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

Smeester¹,

Moriarity²,

Beitz³

2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks efective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of beter therapies for reducing pain in osteosarcoma patients. Studies are underway to deine the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will signiicantly decrease bone cancer pain.

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

Cited by 68 publications

References 20 publications

The prognostic significance of BMP-6 signaling in prostate cancer

The prognostic significance of BMP-6 signaling in prostate cancer

Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

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