• Journal of Life Science
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• v.26 no.10
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• pp.1189-1195
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• 2016

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. To enable migration and invasion, cells must proliferate and secrete proteinases, which degrade the surrounding extracellular matrix. The goal of this study was to investigate the cell proliferation; matrix metalloproteinase-2 (MMP-2), MMP-9, and plasmin secretion; and migration and invasion of glioma-derived U-373-MG cells induced by VEGF and HGF treatment. An additional goal was to test the hypothesis that elevated secretion of MMP-2, MMP-9, and plasmin contributed directly or indirectly to the proliferation, migration, and invasion of U-373-MG cells. Cell proliferation, migration, and invasion and MMP-2, MMP-9, and plasmin secretion were significantly increased in the VEGF and HGF-treated U-373-MG cells. To elucidate the role of the increased secretion of MMP-2, MMP-9, and plasmin in cell proliferation, migration, and invasion of the U-373-MG cells, they were treated with MMPs inhibitor (BB-94) and plasmin inhibitor (α2AP) prior to VEGF or HGF stimulation. The BB-94 and α2AP treatment resulted in a significant reduction in the cell proliferation, migration, and invasion of the U-373-MG cells as compared with the VEGF- and HGF-treated groups. The results indicate that inhibition of MMPs and plasmin reduce the cell proliferation, migration, and invasion of U-373-MG cells.

• Archives of Plastic Surgery
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• v.36 no.4
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• pp.417-421
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• 2009

Purpose: Dermatofibrosarcoma protuberans(DFSP) is a moderate - degree malignant tumor of soft tissue from dermis to fat layer with high recurrences(11% to 73%) due to its local infiltrative characteristic. Many debates and controversies in deciding accurate surgical margin were presented before, but references about depth of invasion and appropriate surgical excision level were not properly made out. Therefore, we tried to identify the degree of tissue invasion of DFSP. Methods: Twenty patients, including 8 patients with recurrent lesions, over last 10 years were reviewed retrospectively. Different surgical margins were applied according to the location and based on histopathologic result, we have defined as a 'deep tissue invasion' if there were infiltration of tumor cell into fascia or underlying muscle layer was present. All invaded tissue including dermis, fat, fascia and muscle were excised until no tumor cell was found during intraoperative frozen section biopsy. And comparative analysis of deep tissue invasion according to age, primary site, duration of disease and recurrence was done. Results: Thirteen patients(65%) showed deep tissue invasion and incidence was found to be increasing with age(over 30 years old). All patients with DFSP on head and neck region revealed deep tissue invasion followed by trunk(54%) and lower extremities(50%). There was no relationship between duration of disease and deep tissue invasion. Conclusions: It is clear that many cases of DFSP had a deep tissue invasion. And high prevalence of deep tissue invasion with age, primary site was intimately associated. So, underlying deep tissue must be completely examined and excised sufficiently throughout the operation for clear resection of DFSP with no recurrences, especially when age is over 30s and on head and neck region.

• BMB Reports
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• v.52 no.8
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• pp.490-495
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• 2019

Using tunneling nanotubes (TNTs), various pathological molecules and viruses disseminate to adjacent cells intercellularly. Here, we show that the intracellular invasion of Mycoplasma hyorhinis induces the formation of actin- and tubulin-based TNTs in various mammalian cell lines. M. hyorhinis was found in TNTs generated by M. hyorhinis infection in NIH3T3 cells. Because mycoplasma-free recipient cells received mycoplasmas from M. hyorhinis-infected donor cells in a mixed co-culture system and not a spatially separated co-culture system, direct cell-to-cell contact via TNTs was necessary for the intracellular dissemination of M. hyorhinis. The activity of Rac1, which is a small GTP binding protein, was increased by the intracellular invasion of M. hyorhinis, and its pharmacological and genetic inhibition prevented M. hyorhinis infection-induced TNT generation in NIH3T3 cells. The pharmacological and genetic inhibition of Rac1 also reduced the cell-to-cell dissemination of M. hyorhinis. Based on these data, we conclude that intracellular invasion of M. hyorhinis induces the formation of TNTs, which are used for the cell-to-cell dissemination of M. hyorhinis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.427-432
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• 2014

Isocitrate dehydrogenase (IDH) is of great importance in cell metabolism and energy conversion. IDH mutation in glioma cells is reported to be associated with an increased overall survival. However, effects biological behavior of therapy of gliomas are unclear. Here, we investigated the influence of wild-type and mutated IDH genes on glioma cell biological behavior and response to chemotherapy. Relevant mechanisms were further explored. We designed our study on the background of the IDHR132H mutation. Stable cell lines were constructed by transfection. The CCK-8 method was used to assess cell proliferation, flow cytometry for the cell cycle and cell apoptosis, and the transwell method for cell invasion. Nude mouse models were employed to determine tumorigenesis and sensitivity to chemotherapy. Western blotting was used to detect relevant protein expression levels. We found that overexpression of wild IDH1 gene did not cause changes in the cell cycle, apoptosis and invasion ability. However, it resulted in chemotherapy resistance to a high dose of temozolomide (TMZ) in vivo and in vitro. The IDH1 mutation caused cell cycle arrest in G1 stage and a reduction of proliferation and invasion ability, while raising sensitivity to chemotherapy. This may provide an explanation for the better prognosis of IDH1 mutated glioma patients and the relative worse prognosis of their wild-type IDH1 counterparts. We also expect IDH1 mutations may be optimized as new targets to improve the prognosis of glioma patients.

• BMB Reports
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• v.46 no.11
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• pp.533-538
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• 2013

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1845-1849
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• 2012

Objective: Tissue factor (TF) is expressed abnormally in certain types of tumor cells, closely related to invasion and metastasis. The aim of this study was to construct a human gastric cancer cell line SGC7901 stably-transfected with human TF, and observe effects on oxaliplatin-dependent inhibition of invasion and the apoptosis induction. Methods: The target gene TF was obtained from human placenta by nested PCR and introduced into the human gastric cell line SGC7901 through transfection mediated by lipofectamine. Stably-transfected cells were screened using G418. Examples successfully transfected with TF-pcDNA3 recombinant (experimental group), and empty vector pcDNA3 (control group) were incubated with oxaliplatin. Transwell chambers were used to show change in invasive ability. Caspase-3 activity was detected using a colorimetric method and annexin-V/PI double-staining was applied to detect apoptosis. Results: We generated the human gastric cancer cell line SGC7901/TF successfully, expressing TF stably and efficiently. Compared with the control group, invasion increased, whereas caspase-3 activity and apoptosis rate were decreased in the experimental group. Conclusion: TF can enhance the invasive capacity of gastric cancer cells in vitro. Its increased expression may reduce invasion inhibition and apoptosis-inducing effects of oxaliplatin and therefore may warrant targeting for improved chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2859-2863
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• 2013

Polyphenolic compounds from pomegranate fruit extracts (PFEs) have been reported to possess antiproliferative, pro-apoptotic, anti-inflammatory and anti-invasion effects in prostate and other cancers. However, the mechanisms responsible for the inhibition of cancer invasion remain to be clarified. In the present study, we investigated anti-invasive effects of ellagic acid (EA) in androgen-independent human (PC-3) and rat (PLS10) prostate cancer cell lines in vitro. The results indicated that non-toxic concentrations of EA significantly inhibited the motility and invasion of cells examined in migration and invasion assays. The EA treatment slightly decreased secretion of matrix metalloproteinase (MMP)-2 but not MMP-9 from both cell lines. We further found that EA significantly reduced proteolytic activity of collagenase/gelatinase secreted from the PLS-10 cell line. Collagenase IV activity was also concentration-dependently inhibited by EA. These results demonstrated that EA has an ability to inhibit invasive potential of prostate cancer cells through action on protease activity.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.161-169
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• 2018

We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.

• Genomics & Informatics
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• v.12 no.1
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• pp.12-20
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• 2014

The epithelial-mesenchymal transition (EMT) is one mechanism by which cells with mesenchymal features can be generated and is a fundamental event in morphogenesis. Recently, invasion and metastasis of cancer cells from the primary tumor are now thought to be initiated by the developmental process termed the EMT, whereby epithelial cells lose cell polarity and cell-cell interactions, and gain mesenchymal phenotypes with increased migratory and invasive properties. The EMT is believed to be an important step in metastasis and is implicated in cancer progression, although the influence of the EMT in clinical specimens has been debated. This review presents the recent results of two cell surface proteins, the functions and underlying mechanisms of which have recently begun to be demonstrated, as novel regulators of the molecular networks that induce the EMT and cancer progression.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.76-80
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• 1998

Generally, the papillary carcinoma generally has a favorable prognosis, and several variants of pathologic heterogeneity are recognized. Variants that are regarded as more aggressive are tall cell, columnar cell, and diffuse sclerosing types. Seventeen cases of papillary thyroid carcinoma showing clinically aggressive behavior, invading extrathyroidal structures, were retrospectively reviewed to evaluate the morphological variants of the tumors. Six of them were found to be pure papillary and nine were mixed types regarded as non-aggressive variants. Four cases were found to be tall cell variants, two cases of non-extrathryoidal invasion and two of extrathyroidal invasion regarded as aggressive variants. Our findings suggest that the prognosis of papillary carcinoma not always be based on its morphological variant and more attention should be given to other clinical parameters.