Seven BMPs and all their receptors are simultaneously expressed in osteosarcoma cells

Gobbi, Giuliana; Sangiorgi, Luca; Lenzi, Luca; Casadei, Raffaella; Canaider, Silvia; Strippoli, Pierluigi; Lucarelli, Enrico; Ghedini, I.; Donati, Davide María; Fabbri, Nicola; Warzecha, J.; Yeoung, Choh; Helman, Lee J.; Picci, Piero; Carinci, Paolo

doi:10.3892/ijo.20.1.143

Cited by 40 publications

(42 citation statements)

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“…Therefore, BMPs, BMPRs and Smads have been considered to be important factors for suppression, rather than progression or metastasis, of prostate and cutaneous tumors [14,18,22]. However, expressions of BMPs and their receptors have been confirmed in a human osteosarcoma cell line, suggesting a mechanism involving the simultaneous activation of BMPs and BMPRs in osteosarcoma [8]. In addition, expression of BMP-2 and BMPR II in osteosarcoma has been shown to be associated with poor prognosis [10,41].…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Cell Line, MCO-Y4, Derived from Canine Mammary Gland Osteosarcoma

Kawabata

Yamamoto

Lan

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. A cell line, MCO-Y4, was established from a mammary gland osteosarcoma of a 16-year-old female mongrel dog. Histopathologically the tumor was composed of osteoblastic cells with an osteoid meshwork and chondroid matrix. The mean doubling time of the cells at the 93rd passage was 32.39 ± 4.66 hr. Immunohistochemically, the osteoblastic and chondroblastic cells were positive for bone morphogenetic protein (BMP)-2/4 and BMP receptor (BMPR) II. The cultured cells were spindle in shape during the growth and the confluent phases. No tumor matrix was detected in the culture dish by alcian blue staining or von-Kossa silver impregnation. MCO-Y4 cells on the chamber slides showed intense immunoreactivity for BMP-2/4 and BMPR II. Noggin, an antagonist for BMP-2/ 4, showed the growth inhibition on MCO-Y4 cells. In addition, fibronectin might be potential for stimulating growth of MCO-Y4 cells. When transplanted into severe combined immunodeficiency mice, the cells formed tumors consisting of solid proliferation of osteoblastic and fibroblastic cells with woven-bone trabeculae. These tumor cells were intensely positive for BMP-2/4 and BMPR II. Our results suggested that the cell line might be useful for studying the role of BMPs in canine osteosarcoma and the mechanism of ossification. KEY WORDS: bone morphogenetic protein, canine mammary gland, cell line, noggin, osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Cell Line, MCO-Y4, Derived from Canine Mammary Gland Osteosarcoma

Kawabata

Yamamoto

Lan

et al. 2006

The Journal of Veterinary Medical Science

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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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“…6 Constitutive expression of BMP is not restricted to malignant melanoma cells. BMP mRNAs are expressed in a variety of human carcinoma cell lines: osteosarcoma, 9 salivary adenocarcinoma, 10 prostate, 11 pancreas, 12 ovarian 13 and breast. 14 Moreover, BMP-2 stimulates angiogenesis in developing tumors formed from A549 lung cancer cells injected into athymic nude mice.…”

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confidence: 99%

Noggin blocks invasive growth of murine B16‐F1 melanoma cells in the optic cup of the chick embryo

Busch¹,

Drews²,

Eisele³

et al. 2007

Intl Journal of Cancer

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Melanoma cells originate from the neural crest and are characterized by high migratory potential and invasive growth. After transplantation into the neural tube of the chick embryo, melanoma cells spontaneously emigrate along the neural crest pathways without tumor formation or malignant growth. This emigration depends on the constitutive over-expression of bone morphogenetic protein-2 (BMP-2) and can be ablated by the BMP-antagonist noggin. When transplanted into the embryonic optic cup, melanoma cells invade the host tissue and form malignant tumors. Here, we asked if the invasive growth of melanoma cells in the optic cup could be influenced by BMP-2 or noggin. Mouse B16-F1 cells were grown as aggregates, treated with BMP-2 or noggin during aggregation and transplanted into the optic cup of 3-day chick embryos. After 3 days of subsequent incubation, embryos were evaluated for melanoma cell invasiveness. Immunohistochemical examination revealed that untreated and BMP-2-treated melanoma cells had grown malignantly into the host tissue. However, noggin pretreatment of the aggregates had blocked melanoma cell invasiveness and tumor formation. We conclude that invasive growth of melanoma cells in vivo is BMP-dependent and can be ablated by noggin, thus rendering noggin a promising agent for the treatment of BMP-over-expressing melanoma. ' 2007 Wiley-Liss, Inc.

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Seven BMPs and all their receptors are simultaneously expressed in osteosarcoma cells

Cited by 40 publications

References 0 publications

Establishment and Characterization of a Cell Line, MCO-Y4, Derived from Canine Mammary Gland Osteosarcoma

Establishment and Characterization of a Cell Line, MCO-Y4, Derived from Canine Mammary Gland Osteosarcoma

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

Noggin blocks invasive growth of murine B16‐F1 melanoma cells in the optic cup of the chick embryo

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