Bone morphogenetic protein-2 and tumor growth: Diverse effects and possibilities for therapy

Tian, Haijun; Zhao, Jie; Brochmann, Elsa J.; Wang, Jeffrey C.; Murray, Samuel S.

doi:10.1016/j.cytogfr.2017.01.002

Cited by 35 publications

(36 citation statements)

References 106 publications

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“…In an effort to provide a clear and practical summary of the roles of BMP‐2 so that clinicians can make informed decisions regarding the use of exogenous BMP‐2 and pursue the use of BMP agonists and antagonists as potential therapeutics, our group has recently published a comprehensive review . A prominent finding in our review was that those works that hypothesize an inhibitory effect for BMP‐2 most often examined only the proliferative properties of the tumor cells, whereas the papers that hypothesized a promotive effect were often more comprehensive and examined the effects of BMP‐2 on invasiveness and migration of tumor cells as well . Many authors reported opposing results pertaining to the effects of BMP‐2 on tumor growth when proliferation testing alone was employed.…”

Section: Discussionmentioning

confidence: 99%

“…Since approved for clinical use by FDA in 2002, BMP‐2 has been used as a substitute for bone auto graft or allograft, yielding superior fusion results . The relationship between BMP‐2 and tumor growth has gained increasing interest in the recent years, especially after Carragee et al raised concerns with respect to tumor formation in association with the use of BMP‐2 in spine surgery, However, there is still no consensus regarding either the safety of exogenously delivered BMP‐2 or the role of endogenous BMP‐2 in autocrine stimulation of tumor growth . The effects of BMP‐2 on osteosarcoma are of particular interest to orthopaedic surgeons.…”

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confidence: 99%

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Bone morphogenetic protein‐2 promotes osteosarcoma growth by promoting epithelial‐mesenchymal transition (EMT) through the Wnt/β‐catenin signaling pathway

Tian

Zhou

Chen

et al. 2019

Journal Orthopaedic Research

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The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/b-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while b-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3a and p-GSK-3b were also significantly upregulated indicating that the Wnt/b-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/b-catenin signaling pathway. ß

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bone morphogenetic protein‐2 promotes osteosarcoma growth by promoting epithelial‐mesenchymal transition (EMT) through the Wnt/β‐catenin signaling pathway

Tian

Zhou

Chen

et al. 2019

Journal Orthopaedic Research

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“…[ 5,6 ] However, overdose of BMP‐2 may cause uncontrolled bone formation, soft tissue inflammation, and even carcinogenesis. [ 7 ] To overcome such issues, controlled and sustained GF release systems have been extensively studied. [ 3,4,8 ] One of the primary approaches is to encapsulate GFs within polymeric matrix as to protect them from degradation.…”

Section: Introductionmentioning

confidence: 99%

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

Jiang

Zhou

et al. 2020

Adv Healthcare Materials

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Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as therapeutics is limited by their short half‐life within the physiological microenvironment and significant side effects caused by off‐target effects or improper dosage. “Smart” materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on‐demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these “smart” materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease‐specific stimuli. The aim of this review is to summarize the current research on stimuli‐responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such “smart” materials and perspectives on future applications of stimuli‐responsive GF delivery for tissue regeneration are also discussed.

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“…[9] Native tissues show mechanical properties that vary from effective elastic moduli of 0.1 kPa in "soft" neural tissues to effective elastic moduli of 20 million times higher in stiff ("hard") bony tissues. [32] Understanding the dynamic state of the tumor microenvironment regarding the homotypic or heterotypic cell-cell interaction and spatiotemporal regulation of ECM components has been a huge challenge over years. [31] Such enzymatic degra-dation breakdown the connective tissues, playing a crucial role in tumor development, invasion, and metastasis.…”

Section: Role Of Microenvironment In Tumor Pathophysiology and Therapmentioning

confidence: 99%

“…For example, high levels of MMP-2 are verified in several cancer types, including OS, and are associated with poor prognosis and enhanced invasiveness. [32] Understanding the dynamic state of the tumor microenvironment regarding the homotypic or heterotypic cell-cell interaction and spatiotemporal regulation of ECM components has been a huge challenge over years. In this sense, the faithful recapitulation of the in vivo microenvironment has been a focus of the scope of tissue engineering.…”

Section: Role Of Microenvironment In Tumor Pathophysiology and Therapmentioning

confidence: 99%

Three‐Dimensional Osteosarcoma Models for Advancing Drug Discovery and Development

Monteiro

Custódio

Mano

2018

Advanced Therapeutics

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Osteosarcoma (OS) is the most common primary malignant tumor of bone that mainly affects children and adolescents. The currently available therapies are not effective and the search for new OS anticancer drugs is extremely urgent. Understanding the mechanisms that underlie the tumor progression, invasion, and metastasis is an essential step toward effective cancer therapies. Tissue engineering has given a great contribution to the development of reliable and cost-effective platforms for drug screening and validation through 3D in vitro models that more faithfully mimic the in vivo pathophysiology than conventional 2D models. The progress in the field of functional and biomimetic biomaterials in the development of 3D tissue models has provided tools for a close recapitulation of the highly complex and dynamic tumor microenvironment. This review focuses on the most recent advances in 3D in vitro osteosarcoma models, highlighting the crucial role of the extracellular matrix and stromal cells in tumor progression, how they contribute to drug resistance and disease prevalence, and the future pathways toward an effective and personalized model for drug screening and validation.

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Bone morphogenetic protein-2 and tumor growth: Diverse effects and possibilities for therapy

Cited by 35 publications

References 106 publications

Bone morphogenetic protein‐2 promotes osteosarcoma growth by promoting epithelial‐mesenchymal transition (EMT) through the Wnt/β‐catenin signaling pathway

Bone morphogenetic protein‐2 promotes osteosarcoma growth by promoting epithelial‐mesenchymal transition (EMT) through the Wnt/β‐catenin signaling pathway

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

Three‐Dimensional Osteosarcoma Models for Advancing Drug Discovery and Development

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