• BMB Reports
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• 제48권3호
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• pp.127-128
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• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.1997-2006
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• 2015

Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.

• Journal of Periodontal and Implant Science
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• 제27권1호
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• pp.111-116
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• 1997

The oral cavity is easily accessible for direct exposure of a malignant disease. 1 percent of the oral malignant tumors are of metastatic origin and approximately 10 percent to 25 percent of the 1 percent fraction originate from the lungs. A case of metastatic lung carcinoma to the gingiva in a 88-year-old male is reported. He complained of pain and swelling between right maxillary 1st premolar and 2nd molar. Although surgical excision of the lesion has been done, the gingival lesion developed as a quickly growing mass and recurred 2 weeks after surgical excision. The gingival mass was histopathologically diagnosed as an undifferentiated carcinoma. Epithelial layer was continuous without ulceration and it seems that the cancer cells are originated from primary tumor. Infiltrated cancer cells were pleomorphic and dyskeratotic. The cells had 2 or more nuclei, not showing squamous or glandular differentiation. Immunohistochemical study revealed the cells originated from the epithelial cells. The prognosis is poor, because prognosis depends on surgical elimination of the primary tumor.

• 대한세포병리학회지
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• 제9권1호
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• pp.111-115
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• 1998

Although the characteristic cytologic features of melanoma have been well described the diagnosis of metastatic melanoma by fine needle aspiration cytology (FNAC) may be difficult in the case of amelanotic melanoma and in the absence of awareness of clinical history. Furthermore, when the breast is the site of initial presentation, it could simulate a primary breast carcinoma leading to misdiagnosis. The recognition of metastatic malignant melanoma in FNAC material is essential to avoid an unnecessary mastectomy and to ensure appropriate chemotherapy. We experienced a case of metastatic melanoma of breast which presented as solitary breast mass in a 56-year-old woman. She had a history of surgical excision of right foot for melanoma one year ago. The cytologic smears were composed of noncohesive epithelioid cells with round or eccentric nuclei, bi-or multi-nucleation, prominent nucleoli, fine chromatin, and intranuclear inclusions. The cytoplasm of tumor cells had scanty melanin pigment but were diffusely positive for S-100 protein.

• 대한세포병리학회지
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• 제19권2호
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• pp.72-85
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• 2008

Cytologic examination of the body cavity fluid is very important because the specimens represent a significant percentage of nongynecologic samples and this cytologic examination may be the first, best or only chance for making the diagnosis of an underlying malignancy. The purposes of body cavity fluid examination are to correctly identify cancer cells and if possible, to identify the tumor types and primary sites when presented with unknown primary tumor sites. The most important basic differential diagnosis is that of benign and reactive disease vs malignant disease. Reactive mesothelial cells are a consistent population in body cavity fluid, and these are the most versatile cells in the body. Due to the specific environment of the body cavity, the exfoliated reactive mesothelial cells may show significant morphologic overlap with the morphology of cancer cells. With a focus on the differential points between reactive mesothelial cells and metastatic adenocarcinoma cells, the practical diagnostic approaches, the diagnostic clues and the pitfalls to achieve a correct diagnosis are presented in this review.

• Journal of Microbiology and Biotechnology
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• 제14권5호
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• pp.891-900
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• 2004

UDP-N-Acetylglucosamine(GlcNAc):$\beta$1,4-D-mannoside$\beta$-l ,4N-acetylglucosaminyltransferase-III (GnT-III) and UDP-N-GlcNAc:$\alpha$-6-D-mannosid$\beta$-1,6N-acetylglucosaminyltransferase-V(GnT - V) activities were determined in human hepatoma cell lines and metastatic colon cancer cells, and their activities were compared with those of normal liver cells and fetal hepatocytes. GnT-III activities were higher than those of GnT-V in hepatic carcinoma cells. When the two enzyme activities were assayed in highly metastatic colon cancer cells, GnT - V activities were much higher than those of GnT-III. When GlcN, GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzymes displayed different kinetic properties between hepatic and colon cancer cells, depending on their metastatic potentials. Normal cells of two origins had characteristically very low levels of GnT-III and -V activities, whereas hepatoma and colon cancer cells contained high levels of activities. These data were supported by RT-PCR and Northern blot analyses, showing that the expression of GnT-III and -V mRNAs were increased in proportion to the enzymatic activities. The increased GnT-III, md -V activities were also correlated with increased glycosylation of the cellular glycoproteins in hepatoma and colon cancer cells, as examined by lectin blotting analysis by using wheat germ glutinin (WGA), erythroagglutinating phytohemagglutinin (E-PHA), leukoagglutinating phytohemagglutinin (L-PHA), and concanavalin A (Con A). Treatment with retinoic acid, a differentiation agent, resulted in decreases of both GnT-III and -V activities of HepG2 and HepG3 cells. In colon carcinoma cells, however, treatment with retinoic acid resulted in a reduction of GnT-V activity, but not with GnT-III activity. Although the mechanism underlying the induction of these mzymes is unclear, oligosaccharides in many glycoproteins have been observed of cancer cells.

• 대한세포병리학회지
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• 제14권1호
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• pp.36-41
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• 2003

Epithelioid hemangioendothelioma is a rare vascular tumor of borderline malignancy which is characterized by the presence of "epithelioid" or "histiocytoid" endothelial cells. Superficial and deep tumors have been recognized in the extremities, head, neck, chest, and mediastinum of adult patients. It may also occur as a primary tumor of liver, bone, and other visceral organs. Few effusion cytologic findings of epithelioid hemangioendothelioma have been reported. We report a case of composite epithelioid hemangioendothelioma with focal epithelioid angiosarcomatous areas of the iliac bone and adjacent soft tissue in a 38-year-old female, which, during its metastatic course, was presented as a pleural effusion. The effusion was cellular with epithelioid cells presenting both singly and in clusters. The tumor cells were round to ovoid shewing cytoplasmic vacuolization, variability in cell size, and prominent nucleoli. The effusion smears and cell block sections revealed strong positive staining for CD31 and vimentin, weak positive for CD34 and Factor VIII-related antigen, and negative for cytokeratin, CEA, and calretinin. The cytologic findings in this case were similar to that of metastatic adenocarcinoma or malignant mesothelioma. Therefore, immunocytochemical staining in smear and cell block is a helpful tool to differentiate malignant 'epithelioid' cells in effusion.

• 대한세포병리학회지
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• 제4권2호
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• pp.171-175
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• 1993

Synovial sarcoma us a rare malignant neoplasm of the soft tissue arising in the lower extremity, inguinal area, and upper arm. The majority occurs in patients between the age of 15 and 40 years. The histologic diagnosis is based on the classical biphasic type with the distinct epithelial and spindle cell components. We have recently encountered a case of metastatic synovial sarcoma of the lung diagnosed by fine needle aspiration cytology. A 34-year-old man was admitted because of a palpable mass on the antero-lateral side of the right tibia for 3 years. On admission, a well demarcated metastatic pulmonary nodule, measuring 5 cm in diameter, was also identified in the simple chest X-ray. Resection of the lower leg mass revealed typical histologic features of biphasic synovial sarcoma. Aspiration cytology of the pulmonary nodule revealed numerous clusters of spindle cells admixed with groups of epithelial cells. The epithelial cells had moderate-sized, round to oval shaped, and hyperchromatic nuclei. The cytoplasm was clear, but not distinctive. Interspersed tell elements were fibroblast-like spindle cells having elongated hyperchromatic nuclei.

• Nutrition Research and Practice
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• 제8권5호
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3519-3528
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• 2012

Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for the treatment of cancers, on metastatic potential of highly metastatic B16F10 melanoma cells were investigated in vitro. Cell proliferation was assessed using the MTT colorimetric assay. Details of metastatic capabilities including invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden Chamber invasion and migration, scratch motility and cell attachment assays, respectively. The results demonstrated that n-hexane and chloroform extracts exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity-guided chromatographic fractionation of both active n-hexane and chloroform extracts led to the isolation of two main prenylated xanthones and characterization as macluraxanthone and gerontoxanthone-I, respectively, their structures being identified by comparison with the spectral data. Interestingly, both exhibited potent effective effects. At non-toxic effective doses, n-hexane and chloroform extracts (10 and $30{\mu}g/ml$) as well as macluraxanthone and gerontoxanthone-I (3 and $10{\mu}M$) significantly inhibited B16F10 cell invasion, to a greater extent than $10{\mu}m$ doxorubicin, while reducing migration of cancer cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells to high concentrations of chloroform ($30{\mu}g/ml$) and geratoxanthone-I ($20{\mu}M$) for 24 h resulted in delayed adhesion and retarded colonization. As insights into mechanisms of action, typical morphological changes of apoptotic cells e.g. membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow cytometry were observed, suggesting DNA damage and subsequent apoptotic cell death. Taken together, our findings indicate for the first time that active n-hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis processes including proliferation, adhesion, invasion and migration, possibly through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based on these data, M. amboinensis Bl. represents a potential candidate novel chemopreventive and/or chemotherapeutic agent. Additionally, they also support its ethno-medicinal usage for cancer prevention and/or chemotherapy.