• BMB Reports
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• v.36 no.1
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• pp.128-137
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• 2003

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1321-1326
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• 2014

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.32-32
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• 1999

No Abstract, See Full Text

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3865-3871
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• 2014

It is becoming progressively more understandable that different phytochemicals isolated from edible plants interfere with specific stages of carcinogenesis. Cancer cells have evolved hallmark mechanisms to escape from death. Concordant with this approach, there is a disruption of spatiotemproal behaviour of signaling cascades in cancer cells, which can escape from apoptosis because of downregulation of tumor suppressor genes and over-expression of oncogenes. Genomic instability, intra-tumor heterogeneity, cellular plasticity and metastasizing potential of cancer cells all are related to molecular alterations. Data obtained through in vitro studies has convincingly revealed that curcumin, EGCG, resveratrol and quercetin are promising anticancer agents. Their efficacy has been tested in tumor xenografted mice and considerable experimental findings have stimulated researchers to further improve the bioavailability of these nutraceuticals. We partition this review into different sections with emphasis on how bioavailability of curcumin, EGCG, resveratrol and quercetin has improved using different nanotechnology approaches.

• BMB Reports
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• v.54 no.1
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• pp.44-58
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• 2021

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

• BMB Reports
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• v.54 no.7
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• pp.344-355
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• 2021

Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this mini-review, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.509-518
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• 2017

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor in adults and has poor prognosis. The GBM-specific tumor microenvironment (TME) plays a crucial role in tumor progression, immune escape, local invasion, and metastasis of GBM. Here, we demonstrate that hypoxia, reactive oxygen species (ROS), and differential concentration of glucose influence the expression of cytokines and chemokines, such as IL-6, IL-8, and IP-10, in human glial cell lines. Treatment with cobalt chloride ($CoCl_2$) and hydrogen peroxide ($H_2O_2$) significantly increased the expression levels of IL-6, IL-8, and IP-10 in a dose-dependent manner in CRT-MG and U251-MG astroglioma cells, but not in microglia cells. However, we found strikingly different patterns of expression of cytokines and chemokines between $H_2O_2$-treated CRT-MG cells cultured in low- and high-glucose medium. These results suggest that astroglioma and microglia cells exhibit distinct patterns of cytokine and chemokine expression in response to $CoCl_2$ and $H_2O_2$ treatment, and different concentrations of glucose influence this expression under either hypoxic or oxidant-enriched conditions.

• Biomedical Science Letters
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• v.20 no.3
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• pp.103-110
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• 2014

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They are multidomain proteins and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs). The uncontrolled regulation of MMPs is involved in various pathologic processes, such as tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Especially, matrix metalloproteinase-9 (MMP-9) is one of the metastasis-accelerating genes involved in metastasis of various types of human cancers. Here, we review the member of MMP family and discusses their domain structure and function, enzyme activation, the mechanism of inhibition by TIMPs. In particular, we focus the role of MMP-9 in relation to cancer metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3635-3638
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• 2015

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5181-5186
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• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.