Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma inï¿½vitro

Kim, Jong Bin; Lee, Seulki; Kim, Hye Ri; Park, Seo‐Young; Lee, Minjong; Yoon, Jung‐Hwan; Kim, Yoon Jun

doi:10.3892/ol.2018.8441

Cited by 8 publications

(7 citation statements)

References 35 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In primary lung cancer cells, TGF-β exposure led to an increase in cancer stem cell population through repression of miRNA138 [ 113 ] while in colon cancer, TGF-β seems to play a key role in angiogenesis, tumor growth and metastasis [ 114 ]. On the other hand, in the context of hepatocellular carcinoma, TGF-β resulted in a decrease in cell survival of stem-like side populations [ 115 ]. Collectively, these studies highlight the importance of HIFs and TGF-β in the regulation of EMT, and provide support for the development of strategies exploiting these pathways to overcome therapy resistance.…”

Section: Emt At the Crossroad Of Stemnessmentioning

confidence: 99%

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity

Terry

Zaarour

Venkatesh

et al. 2018

IJMS

View full text Add to dashboard Cite

Hypoxia, or gradients of hypoxia, occurs in most growing solid tumors and may result in pleotropic effects contributing significantly to tumor aggressiveness and therapy resistance. Indeed, the generated hypoxic stress has a strong impact on tumor cell biology. For example, it may contribute to increasing tumor heterogeneity, help cells gain new functional properties and/or select certain cell subpopulations, facilitating the emergence of therapeutic resistant cancer clones, including cancer stem cells coincident with tumor relapse and progression. It controls tumor immunogenicity, immune plasticity, and promotes the differentiation and expansion of immune-suppressive stromal cells. In this context, manipulation of the hypoxic microenvironment may be considered for preventing or reverting the malignant transformation. Here, we review the current knowledge on how hypoxic stress in tumor microenvironments impacts on tumor heterogeneity, plasticity and resistance, with a special interest in the impact on immune resistance and tumor immunogenicity.

show abstract

Section: Emt At the Crossroad Of Stemnessmentioning

confidence: 99%

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity

Terry

Zaarour

Venkatesh

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…These effects are reversed by the treatment with Galunisertib. Another work reported that the expression of CD133 and Vimentin was upregulated by treatment with the TGF-β receptor antagonist SB431542 [23]. Additionally, it was observed by Rani and colleagues that treatment with Galunisertib in vitro modulates the expression of stemness-related genes in invasive HCC cells (HLE and HLF) reducing the expression of CD44 and THY1 and consequently results in decrease in colony formation, liver spheroids and invasive growth capacity in vitro and in ex vivo human HCC samples [24,25].…”

Section: Introductionmentioning

confidence: 99%

Validation of Hepatocellular Carcinoma Experimental Models for TGF-β Promoting Tumor Progression

Mancarella

Krol

Crovace

et al. 2019

Cancers

View full text Add to dashboard Cite

Transforming growth factor beta (TGF-β) is a pleiotropic cytokine with dual role in hepatocellular carcinoma (HCC). It acts as tumor-suppressor and tumor-promoter in the early and late stage respectively. TGF-β influences the tumor-stroma cross-talk affecting the tumoral microenvironment. Therefore, inhibiting the TGF- β mediated pathway alone and/or in combination with chemotherapeutics represents an important therapeutic option. Experimental models to dissect the role of TGF-β in HCC tumor progression as well as the effectiveness of specific inhibitors are tricky. HCC cell lines respond to TGF-β according to their epithelial phenotype. However, the mesenchymal and more aggressive HCC cell lines in vitro, do not develop tumors when transplanted in vivo, thus hampering the understanding of molecular pathways that dictate outcome. In addition, in this model the native immune system is abolished, therefore the contribution of inflammation in hepatocarcinogenesis is unreliable. Different strategies have been set up to engineer HCC animal models, including genetically modified mice, chemically induced HCC, or hydrodynamic techniques. Patient-derived xenograft is currently probably the most fascinating model, keeping in mind that models cannot mirror all the reality. In this context, we discuss the different available HCC mouse models including our experimental model treated with inhibitor of TGF-β receptor Type I kinase (Galunisertib) and a potential role of exosomes in TGF-β moderated tumor progression of HCC. Unfortunately, no positive results were obtained in our treated orthotopic model because it does not reproduce the critical tumor-stroma interactions of the HCC.

show abstract

“…For example, several studies have reported that ANXA3 activated the JNK signaling pathway of stress-activated proteins in hepatocellular carcinoma (22–24). Furthermore, previous studies have demonstrated that the JNK signaling pathway activated CD133 + glioblastoma stem cell self-renewal to promote hepatocellular carcinoma differentiation (25–27). The JNK signaling pathway plays a significant role in ANXA3-mediated cancer stem cells.…”

Section: Discussionmentioning

confidence: 99%

Expression and significance of Annexin A3 in the osteosarcoma cell lines HOS and U2OS

et al. 2019

View full text Add to dashboard Cite

Annexin A3 (ANXA3) is highly expressed in different types of cancers, but the impact of ANXA3 in bone tumors is still not clear. In the present study, the expression of ANXA3 in osteosarcoma cells was first confirmed by cellular immunofluorescence. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of ANXA3 in osteoblasts in the osteosarcoma cell lines U2OS and HOS. Furthermore, small interfering (si)-RNA were transfected into U2OS and HOS cells via a liposome-mediated method. Then once ANXA3 had been successfully downregulated in U2OS and HOS cells, the cells were collected and total protein was extracted after 48 h of transfection. Western blot analysis was used to confirm successful ANXA3 transfection into osteosarcoma cells and the apoptotic rate of HOS and U2OS was detected by flow cytometry. The expression of ANXA3 in the osteosarcoma cell lines HOS and U2OS were first observed by confocal laser scanning microscopy, and was then detected by RT-qPCR and western blotting. The mRNA and protein levels of ANXA3 in the osteosarcoma cell lines HOS and U2OS were significantly increased compared with osteoblasts, particularly in HOS cells. When siRNA was transfected into HOS and U2OS cells, the protein expression level of ANXA3 was measured via western blotting. The results indicated that the expression of ANXA3 was significantly decreased. In addition, to determine whether ANXA3 knockdown induced cell apoptosis, the present study analyzed the apoptotic rate by flow cytometry. The results revealed that ANXA3 knockdown markedly increased HOS and U2OS cell apoptosis. To the best of our knowledge, the present study is the first to confirm that ANXA3 is highly expressed in the osteosarcoma cell lines HOS and U2OS. In addition, downregulation of ANXA3 expression in HOS and U2OS cells could increase apoptotic ability.

show abstract

Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma inï¿½vitro

Cited by 8 publications

References 35 publications

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity

Validation of Hepatocellular Carcinoma Experimental Models for TGF-β Promoting Tumor Progression

Expression and significance of Annexin A3 in the osteosarcoma cell lines HOS and U2OS

Contact Info

Product

Resources

About