Antimigratory and antimetastatic effect of heparin-derived 4–18 unit oligosaccharides in a preclinical human melanoma metastasis model

2009 ◽  
Vol 102 (12) ◽  
pp. 1265-1273 ◽  
Author(s):  
István Kenessey ◽  
Erika Simon ◽  
Krisztina Futosi ◽  
Bíborka Bereczky ◽  
Andrea Kiss ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Metastatic Potential ◽  
Inhibitory Effect ◽  
Human Melanoma ◽  
Migration And Invasion ◽  
Melanoma Metastasis ◽  
Metastasis Model

SummaryHeparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect.These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.

scholarly journals Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Mélissa Labelle-Côté ◽  
Julie Dusseault ◽  
Salma Ismaïl ◽  
Aude Picard-Cloutier ◽  
Peter M Siegel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Melanoma Cell ◽  
Primary Melanoma ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Migration And Invasion ◽  
Melanoma Cell Proliferation

scholarly journals Ribophorin II promotes cell proliferation, migration, and invasion in esophageal cancer cells in vitro and in vivo

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Yongshun Li ◽  
Changrong Huang ◽  
Qizhou Bai ◽  
Jun Yu
Keyword(s):  
Cell Proliferation ◽  
Esophageal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissues ◽  
Esophageal Cancer Cells ◽  
E Cadherin

AbstractEsophageal cancer is a common digestive tract cancer, which is a serious threat to human health. Ribophorin II (RPN2) is a part of an N-oligosaccharyltransferase complex, which is excessively expressed in many kinds of cancers. In the present study, we explore the biological role of RNP2 in esophageal cancer. First, we found that the expression of RPN2 was higher in esophageal cancer tissues than in adjacent non-tumor tissues, and negatively correlated with E-cadherin expression. RPN2 expression levels in esophageal cancer tissues were positively associated with differentiation and tumor node metastasis (TNM) stage. Furthermore, the expression of RPN2 was increased significantly in esophageal cancer cell lines compared with normal cells. The effect of RPN2 down-regulation on cell proliferation, cell migration, and cell invasion was examined by cell counting kit-8 (CCK8), wound healing assay, and Transwell assay, respectively. Silencing RPN2 effectively inhibited cell proliferation of esophageal cancer cells in vitro and in vivo. Cell migration and invasion were also weakened dramatically by siRPN2 treatment of esophageal cancer cells. In addition, protein expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP-2), and E-cadherin in esophageal cancer cells was determined by Western blot analysis. PCNA, MMP-2, E-cadherin, Snail and phosphorylation-Smad2/3 expression was also regulated notably by siRPN2 treatment. These findings indicate that RPN2 exhibits oncogenetic capabilities in esophageal cancer, which could provide novel insights into esophageal cancer prevention and treatment.

scholarly journals TPPP3 Promotes Cell Proliferation, Invasion and Tumor Metastasis via STAT3/ Twist1 Pathway in Non-Small-Cell Lung Carcinoma

2018 ◽  
Vol 50 (5) ◽  
pp. 2004-2016 ◽  
Author(s):  
Yintao Li ◽  
Menglin Bai ◽  
Yali Xu ◽  
Weiwei Zhao ◽  
Naijia Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Tumor Metastasis ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Background/Aims: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis. Methods: RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo. Results: In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS). Conclusion: Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.

scholarly journals CBMT-46. MICRORNA-206 ATTENUATES GLIOMA CELL PROLIFERATION, MIGRATION, AND INVASION BY BLOCKING THE WNT/β-CATENIN PATHWAY VIA DIRECT TARGETING OF FRIZZLED 7

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi43-vi43
Author(s):  
Yingyi Wang ◽  
Fengqi Zhou ◽  
Chunsheng Zhao
Keyword(s):  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Three Dimensional ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Nude Mouse Model ◽  
Real Time Quantitative Pcr

Abstract Glioma is one of the most frequent primary malignant brain tumours in adults and accumulating evidence has shown that microRNAs (miRNAs) are associated with various types of tumours, including glioma. It is essential to acquire a better understanding of the roles and mechanisms of miRNAs in WNT-driven glioblastoma (GBM). Here, we report that miR-206 inhibited the WNT/β-catenin pathway by directly targeting Frizzled 7 (FZD7) and functioned as a tumour-suppressor in glioma. The expression of miR-206 in human samples and glioma cells was assessed by real-time quantitative PCR (RT-qPCR), fluorescence in situ hybridization (FISH), and histological analysis. Cell Counting Kit-8 (CCK-8), colony formation, EdU, flow cytometry, wound healing, transwell invasion, and three-dimensional migration were performed to observe cellular proliferation, migration, and invasion in vitro. The effects of miR-206 in vivo were investigated using a xenograft nude mouse model. miR-206 expression was significantly downregulated in glioma specimens. FZD7 was confirmed as a direct target of miR-206. GBM cell proliferation, migration, and invasion were blocked by restoring the expression of miR-206. Moreover, intracranial glioma models demonstrated an inhibitory effect of miR-206 on intracranial glioma tumour growth. Our results suggested that miR-206 plays a key role in blocking the WNT/β-catenin signalling pathway by suppressing FZD7 and provides a prospective therapeutic strategy for the treatment of malignant glioma and other WNT-driven tumours.

scholarly journals DPEP1 is a direct target of miR-193a-5p and promotes hepatoblastoma progression by PI3K/Akt/mTOR pathway

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xichun Cui ◽  
Xin Liu ◽  
Qicai Han ◽  
Jianming Zhu ◽  
Jianhao Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mammalian Target Of Rapamycin ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Clinical Prognosis ◽  
Therapeutic Outcomes ◽  
Direct Target

Abstract Hepatoblastoma (HB) is the most common hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Increasing evidence shows that dipeptidase 1 (DPEP1) has pivotal function in tumorigenesis in multiple tumors. However, the expression pattern, biological function, and underlying mechanism of DPEP1 in HB have not been reported. Here we showed that DPEP1 was significantly upregulated and was associated with poor prognosis in HB patients. In vitro and in vivo assays indicated that silencing DPEP1 significantly suppressed HB cell proliferation, migration, and invasion, while DPEP1 overexpression exhibited the opposite effect. In addition, we identified that DPEP1 was a direct target of microRNA-193a-5p (miR-193a-5p). Functional experiments demonstrated that overexpression of miR-193a-5p significantly inhibited cell proliferation and invasion of HB cells, while the inhibitory effect could be reversed by DPEP1 overexpression. Moreover, miR-193a-5p was decreased in HB tumor tissues and associated with a poor clinical prognosis. Mechanistically, our results indicated that the miR-193a-5p/DPEP1 axis participated to the progression of HB via regulating the PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin) signaling. In conclusion, our findings suggest that the miR-193a-5p /DPEP1 axis might be a good prognostic predictor and therapeutic target in HB.

scholarly journals Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jia-Huang Liu ◽  
Qi-Fei Wu ◽  
Jun-Ke Fu ◽  
Xiang-Ming Che ◽  
Hai-Jun Li
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Serum Glucose ◽  
Migration And Invasion ◽  
Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

scholarly journals Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jingpeng Wang ◽  
Shuyuan Li ◽  
Gaofeng Zhang ◽  
Huihua Han
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Volatile Anesthetic ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

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