• BMB Reports
• /
• v.52 no.7
• /
• pp.415-423
• /
• 2019

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades.

• Molecules and Cells
• /
• v.47 no.2
• /
• pp.100010.1-100010.12
• /
• 2024

Recently, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing due to the high prevalence of metabolic conditions, such as obesity and type 2 diabetes mellitus. Steatotic liver is a hotspot for cancer metastasis in MASLD. Altered lipid metabolism, a hallmark of MASLD, remodels the tissue microenvironment, making it conducive to the growth of metastatic liver cancer. Tumors exacerbate the dysregulation of hepatic metabolism by releasing extracellular vesicles and particles into the liver. Altered lipid metabolism influences the proliferation, differentiation, and functions of immune cells, contributing to the formation of an immunosuppressive and metastasis-prone liver microenvironment in MASLD. This review discusses the mechanisms by which the steatotic liver promotes liver metastasis progression, focusing on its role in fostering an immunosuppressive microenvironment in MASLD. Furthermore, this review highlights lipid metabolism manipulation strategies for the therapeutic management of metastatic liver cancer.

• Journal of Life Science
• /
• v.28 no.8
• /
• pp.992-998
• /
• 2018

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

• Development and Reproduction
• /
• v.27 no.4
• /
• pp.167-174
• /
• 2023

Development of hepatocellular carcinoma (HCC) is driven by a multistep and long-term process. Because current therapeutic strategies are limited for HCC patients, there are increasing demands for understanding of immunotherapy, which has made technological and conceptual innovations in the treatment of cancer. Here, I discuss HCC immunotherapy in the view of interaction between liver resident cells and immune cells.

• BMB Reports
• /
• v.46 no.5
• /
• pp.252-257
• /
• 2013

Fibroblast activation protein (FAP) is a specific serine protease expressed in tumor stroma proven to be a stimulatory factor in the progression of some cancers. The purpose of this study was to investigate the effects of FAP knockdown on tumor growth and the tumor microenvironment. Mice bearing 4T1 subcutaneous tumors were treated with liposome-shRNA complexes targeting FAP. Tumor volumes and weights were monitored, and FAP, collagen, microvessel density (MVD), and apoptosis were measured. Our studies showed that shRNA targeting of FAP in murine breast cancer reduces FAP expression, inhibits tumor growth, promotes collagen accumulation (38%), and suppresses angiogenesis (71.7%), as well as promoting apoptosis (by threefold). We suggest that FAP plays a role in tumor growth and in altering the tumor microenvironment. Targeting FAP may therefore represent a supplementary therapy for breast cancer.

• Journal of Ginseng Research
• /
• v.43 no.3
• /
• pp.421-430
• /
• 2019

Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

• Journal of the Korea Convergence Society
• /
• v.10 no.4
• /
• pp.81-89
• /
• 2019

This study was analyzed about the relationship between culture microenvironment and cell differentiation of HPV 16 E6/E7-transfected immortalized oral keratinocyte(IHOK). By the alteration of culture environment, IHOK-EF and IHOK-EFKGM were obtained, and the modulation of cell properties was observed by cell proliferation assay, immunofluorescence, microarray, and quantitative real-time PCR analysis. IHOK-EF losed the properties of epithelial cells and obtained the properties of mesenchymal cells, and in the result of microarray analysis, genes related to the inhibition of differentiation such as IL6, TWIST1, and ID2 were highly expressed in IHOK-EF. When the culture environment was recovered to initial environment, these changes were recovered partially, presenting the return of genes involved in the inhibition of differentiation such as IL6, and ID2, particularly. This study will contribute to understand adjustment aspect for cell surviving according to the change of culture microenvironment in the study for determining the cell characteristic, and facilitate therapeutic approach for human disease by applying surviving study according to the change of cancer microenvironment.

• BMB Reports
• /
• v.56 no.4
• /
• pp.258-264
• /
• 2023

As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as a tumor of uncertain differentiation and has few options for treatment due to its lack of targetable genetic alterations. There are also few cell lines that provide a representative model for UPS, leading to a dearth of experimental research. Here, we established and characterized new cell lines derived from two recurrent UPS tissues. Cells were obtained from UPS tissues by mincing, followed by extraction or dissociation using enzymes and culture in a standard culture environment. Cells were maintained for several months without artificial treatment, and some cell clones were found to be tumorigenic in an immunodeficient mouse model. Interestingly, some cells formed tumors in vivo when injected after aggregation in a non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients shared common histological characteristics. Pathways related to the cell cycle, such as DNA replication, were enriched in both cell clones. Pathways related to cell-cell adhesion and cell-cell signaling were also enriched, suggesting a role of the mesenchymal-to-epithelial transition for tumorigenicity in vivo. These new UPS cell lines may facilitate research to identify therapeutic strategies for UPS.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.5
• /
• pp.1164-1177
• /
• 2024

Esophageal squamous cell carcinoma (ESCC) is among the most common malignant tumors of the digestive tract, with the sixth highest fatality rate worldwide. The ESCC-related dataset, GSE20347, was downloaded from the Gene Expression Omnibus (GEO) database, and weighted gene co-expression network analysis was performed to identify genes that are highly correlated with ESCC. A total of 91 transcriptome expression profiles and their corresponding clinical information were obtained from The Cancer Genome Atlas database. A mitochondria-associated risk (MAR) model was constructed using the least absolute shrinkage and selection operator Cox regression analysis and validated using GSE161533. The tumor microenvironment and drug sensitivity were explored using the MAR model. Finally, in vitro experiments were performed to analyze the effects of hub genes on the proliferation and invasion abilities of ESCC cells. To confirm the predictive ability of the MAR model, we constructed a prognostic model and assessed its predictive accuracy. The MAR model revealed substantial differences in immune infiltration and tumor microenvironment characteristics between high- and low-risk populations and a substantial correlation between the risk scores and some common immunological checkpoints. AZD1332 and AZD7762 were more effective for patients in the low-risk group, whereas Entinostat, Nilotinib, Ruxolutinib, and Wnt.c59 were more effective for patients in the high-risk group. Knockdown of TYMS significantly inhibited the proliferation and invasive ability of ESCC cells in vitro. Overall, our MAR model provides stable and reliable results and may be used as a prognostic biomarker for personalized treatment of patients with ESCC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.3
• /
• pp.1085-1091
• /
• 2014

Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.