STAT3 activation by IL-6 from mesenchymal stem cells promotes the proliferation and metastasis of osteosarcoma

Tu, Bing; Du, Lin; Fan, Qiming; Tang, Zuohua; Tang, Tingting

doi:10.1016/j.canlet.2012.06.006

Cited by 166 publications

(163 citation statements)

References 48 publications

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“…Similar results were also found in a rat model [123]. IL-6 secreted by MSCs could activate STAT3 signaling in OS cells, which in turn augment cell proliferation, migration, invasion, and pulmonary metastasis [124]. Interestingly, IL-6/STAT3 signaling could also respond to MSCs to enhance drug resistance.…”

Section: Stromal Niche: Bone Marrow Mesenchymal Stem Cellsupporting

confidence: 79%

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Mai¹,

Zhang²,

Xie³

et al. 2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma (OS) is the most common malignant primary bone tumor in children and adolescents and features rapid development, strong metastatic ability, and poor prognosis. It has been well established that diverse genetic aberrations and metabolic alterations confer the tumorigenesis and development of OS. The intricate metabolism and vascularization that contributes to the nutrient and structural support for tumor progression should be thoroughly clariied to help us gain novel insights into OS and its clinical diagnoses and treatments. With regard to the complex bone extracellular matrix (ECM) and local cell populations, we intend to illustrate the interrelationship between various microenvironmental signals and the diferent stages of OS evolution. Solid evidence has noted two crucial factors of the OS microenvironment in the acquisition of stem cell phenotypes -transforming growth factor-β1 (TGF-β1) signaling and hypoxia. Diferent cell subtypes in the local environment might also serve as unique contributors that interact with each other and communicate with distant cells, thus participating in local invasion and metastasis. Proper models have been established and improved to reveal the evolutionary footsteps of how normal cells transform into a neoplastic state and progress toward malignancy.

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Section: Stromal Niche: Bone Marrow Mesenchymal Stem Cellsupporting

confidence: 79%

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Mai¹,

Zhang²,

Xie³

et al. 2017

Osteosarcoma - Biology, Behavior and Mechanisms

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“…IL-6 activates STAT3 [36][37][38], therefore, we measured secreted IL-6 levels in the supernatants of control and PIBF knock down HTR-8/SVneo and HT-1080 cells by cytometric bead array. IL-6 production of PIBF-silenced trophoblast cells increased, whereas that of PIBF knock down tumour cells was reduced after 48 hours (Fig.…”

Section: Pibf-induced Proteins Are Responsible For Late Signalling Evmentioning

confidence: 99%

“…STAT3 promotes proliferation, cell growth, invasion, metastasis formation and inhibits apoptosis in tumour cells [34,35,38].…”

Section: Hb-egf Promotes Differentiation Of Trophoblast Cells To An Imentioning

confidence: 99%

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

Halász

Polgar

Berta

et al. 2013

Cell. Mol. Life Sci.

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Invasiveness is a common feature of trophoblast and tumours; however, while tumour invasion is uncontrolled, trophoblast invasion is strictly regulated. Both trophoblast and tumour cells express high levels of the immunomodulatory Progesterone-Induced Blocking Factor (PIBF), therefore, we aimed to test the possibility that PIBF might be involved in invasion. To this aim we used PIBF silenced or PIBF treated trophoblast (HTR8/Svneo, and primary trophoblast) and tumour (HT-1080, A549, HCT116, PC3) cell lines. Silencing of PIBF increased invasiveness as well as MMP-2,-9 secretion of HTR8/SVneo, and decreased those of HT-1080 cells. PIBF induced immediate STAT6 activation in both cell lines. Silencing of IL-4Rα abrogated all the above effects of PIBF, suggesting that invasion-related signalling by PIBF is initiated through the IL-4Rα/PIBF-receptor complex. In HTR-8/SVneo PIBF induced fast, but transient Akt and ERK phosphorylation, whereas in tumour cells PIBF triggered sustained Akt, ERK and late STAT3 activation. The late signalling events might be due to indirect action of PIBF. PIBF induced the expression of EGF and HB-EGF in HT-1080 cells. The STAT3 activating effect of PIBF was reduced in HB-EGF deficient HT-1080 cells, suggesting that PIBF-induced HB-EGF contributes to late STAT3 activation. PIBF binds to the promoters of IL-6, EGF and HB-EGF; however, the protein profile of the protein/DNA complex is different in the two cell lines. We conclude that in tumour cells PIBF induces proteins, which activate invasion signalling, while -based on our previous data -PIBF might control trophoblast invasion by suppressing invasive genes.

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“…In the murine models, human xenografts are introduced via inoculation of cells subcutaneously [121], direct injection into the tibia [122], or subperiosteal injection [123]. Thus generated, these models act as avatars to elucidate optimal drug regimes or as disease models for the evaluation of the role of oncogenic molecules in disease progression, including p53 [121], IL-6/ STAT3 [122], and ROCK1 [124].…”

Section: Primary Bone Malignancymentioning

confidence: 99%

“…Thus generated, these models act as avatars to elucidate optimal drug regimes or as disease models for the evaluation of the role of oncogenic molecules in disease progression, including p53 [121], IL-6/ STAT3 [122], and ROCK1 [124]. Of these, orthotopic models are favored for better approximation to the osseous tumor microenvironment; multimodal positron emission tomography, computed tomography, magnetic resonance imaging, and bioluminescent imaging may be performed to achieve highresolution imaging of tumor interactions with bone [125].…”

Section: Primary Bone Malignancymentioning

confidence: 99%

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Chong

Bao

et al. 2016

Curr Mol Bio Rep

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Xenografting involves the transplantation of human tissue or cells into animal models and is an important tool for regenerative medicine research. Implantation of engineered human bone tissues into animal models, for example, is performed in preclinical evaluations of product safety and efficacy. With the advent of improved experimental methodologies, these models are further being exploited to interrogate molecular mechanisms and physiological interactions in vivo. In parallel to these developments, patient-derived xenograft murine models of cancer are increasingly being studied for various applications in cancer research and therapy; it follows that xenograft models in tissue engineering may be adapted for such approaches. In this review, we first discuss the development of human bone xenograft models to recapitulate physiological states in regenerative medicine. Subsequently, we discuss the use of these techniques for applications in modeling pathological states in skeletal oncology, namely, hematopoietic malignancies, bone metastatic disease, and primary bone malignancy.

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STAT3 activation by IL-6 from mesenchymal stem cells promotes the proliferation and metastasis of osteosarcoma

Cited by 166 publications

References 48 publications

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

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