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Cell Invasiveness (cell + invasiveness)
Selected AbstractsNoggin blocks invasive growth of murine B16-F1 melanoma cells in the optic cup of the chick embryo,,INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Christian Busch Abstract Melanoma cells originate from the neural crest and are characterized by high migratory potential and invasive growth. After transplantation into the neural tube of the chick embryo, melanoma cells spontaneously emigrate along the neural crest pathways without tumor formation or malignant growth. This emigration depends on the constitutive over-expression of bone morphogenetic protein-2 (BMP-2) and can be ablated by the BMP-antagonist noggin. When transplanted into the embryonic optic cup, melanoma cells invade the host tissue and form malignant tumors. Here, we asked if the invasive growth of melanoma cells in the optic cup could be influenced by BMP-2 or noggin. Mouse B16-F1 cells were grown as aggregates, treated with BMP-2 or noggin during aggregation and transplanted into the optic cup of 3-day chick embryos. After 3 days of subsequent incubation, embryos were evaluated for melanoma cell invasiveness. Immunohistochemical examination revealed that untreated and BMP-2-treated melanoma cells had grown malignantly into the host tissue. However, noggin pretreatment of the aggregates had blocked melanoma cell invasiveness and tumor formation. We conclude that invasive growth of melanoma cells in vivo is BMP-dependent and can be ablated by noggin, thus rendering noggin a promising agent for the treatment of BMP-over-expressing melanoma. © 2007 Wiley-Liss, Inc. [source] ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancerJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2007N. Valkovskaya Abstract ADAM8 belongs to a family of transmembrane proteins implicated in cell,cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT-PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis-sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy. [source] Dominant-negative CREB inhibits heparanase functionality and melanoma cell invasionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Rebecca Aucoin Abstract Heparanase (HPSE-1) is an endo-,- d -glucuronidase involved in the degradation of cell-surface/extracellular matrix heparan sulfate (HS) in normal and neoplastic tissues. HPSE-1 represents the first example of purification and cloning of a mammalian HS-degradative enzyme. Elevated HPSE-1 levels are known to be associated with metastatic cancers, directly implicating HPSE-1 in metastatic events. The purpose of this study was to determine the role of cAMP response element-binding protein (CREB) in modulating HPSE-1-mediated effects on human melanoma cell invasion. Highly invasive, brain-metastatic melanoma cells (70W) were transfected with the dominant-negative CREB (KCREB) and subsequently analyzed for changes in their HPSE-1 content, functionality, and cell invasive properties. KCREB-transfected cells showed a decrease in HPSE-1 mRNA expression and activity. This correlated with a significantly decreased invasion of these cells through MatrigelÔ-coated filters. Furthermore, adenoviral vectors containing the full-length human HPSE-1 cDNA in sense orientation (Ad-S/hep) were constructed to investigate CREB effects on HPSE-1. Restoration of HPSE-1 expression and functionality following Ad-S/hep infection of KCREB-transfected 70W cells recovered melanoma cell invasiveness. These results demonstrate that KCREB inhibits HPSE-1 and suggest that one of the roles CREB plays in the acquisition of melanoma cells metastatic phenotype is affecting HPSE-1 activity. © 2004 Wiley-Liss, Inc. [source] Bmi-1 is critical for the proliferation and invasiveness of gastric carcinoma cellsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2010Wei Li Abstract Background and Aim:, Bmi-1 is a transcriptional repressor belonging to the Polycomb group and is associated with the cell proliferation and carcinogenesis of a variety of human cancers. The level of Bmi-1 expression correlates with the aggressiveness of many cancers, and is considered an important marker for cancer diagnosis. However, its role in gastric carcinoma is unknown. Methods:, We used lentiviral mediated interfering short hairpin RNA to knockdown Bmi-1 expression in gastric carcinoma human gastric cancer cell line (AGS cells), then tested the cell proliferation by MTT assay, rate of colony formation by colony formation assay, cell cycle distribution by fluorescence-activated cell sorting and cell invasiveness by cell invasion assay. To analyze the expression and localization of Bmi-1 in gastric tumor tissues, we further performed the immunohistochemistry analysis on a gastric cancer tissue array. Results:, We found that knocking down Bmi-1 led to slower cell growth, lesser cell invasiveness, decelerated colony formation, and altered cell cycle progression. In addition, a positive relationship between nuclear expression of Bmi-1 and gastric cancer was observed, suggesting that nucleus localization of Bmi-1 in the cells may be a novel marker of gastric cancer. Conclusions:, Our study highlights critical roles for Bmi-1 in gastric cancer, and suggests that Bmi-1 nuclear localization could be an important marker for the diagnosis of gastric cancer. [source] Osteopontin is a new target molecule for ovarian clear cell carcinoma therapyCANCER SCIENCE, Issue 8 2010Motoki Matsuura Recent studies have demonstrated overexpression of osteopontin (OPN) in ovarian clear cell carcinoma. Here, we revealed the role of OPN in invasiveness in ovarian clear cell carcinoma. We used immunofluorescence analysis to detect OPN in a total of 160 patient-derived specimens. Ovarian clear cell carcinoma cell lines, RMG-1 and TOV-21G, were used to monitor changes in OPN and integrin levels, and cell invasiveness following treatment with OPN, simvastatin, and transfection with siRNA. Immunofluorescence analysis revealed statistically significant differences among the histological groups, and ovarian clear cell carcinoma expressed a strong OPN signal. The OPN receptors, alpha v and 5, and beta 1 and 3 integrins, were increased after treatment with OPN. Invasion assays indicated that OPN enhanced in vitro extracellular matrix invasion dose-dependently in ovarian clear cell carcinoma. Simvastatin significantly reduced expression of OPN and the integrins, and decreased ECM invasion. RNA interference also suppressed ECM invasion. These results suggest that down- or up-regulation of OPN is involved in carcinoma cell invasion. We thus conclude that OPN regulation could have a crucial role in ovarian clear cell carcinoma therapy. (Cancer Sci 2010) [source] Zebrafish embryo extracts promote sphere-forming abilities of human melanoma cell lineCANCER SCIENCE, Issue 8 2009Yi-Rang Na Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factor receptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-like character. Zebrafish embryo extracts at 50% epiboly stage inhibited melanoma bulk cell proliferation in a dose-dependent manner. However, sphere-forming abilities were significantly enhanced under 1 µg/mL concentration of 50% epiboly stage embryo extract treatment. Our findings implicate that we should consider cell subsets of a different character from the tumor origin that can respond differently to exogenous substances or tumor microenvironments. We suggest that cancer research should consider both minor stem-like subpopulations and the other major bulk tumor cells. (Cancer Sci 2009) [source] Collagens, stromal cell-derived factor-1, and basic fibroblast growth factor increase cancer cell invasiveness in a hyaluronan hydrogelCELL PROLIFERATION, Issue 2 2008L. David Objective: Beyond to control of cell migration, differentiation and proliferation, the extracellular matrix (ECM) also contributes to invasiveness of human cancers. As the roles of hyaluronan (HA) and collagens in this process are still controversial, we have investigated their involvement in cancer pathogenesis. Materials and methods: With this aim in view, we developed a three-dimensional matrix, as reticulate HA hydrogel alone or coated with different collagens, in which cells could invade and grow. Results: We show that cancer cells, which were non-invasive in a single HA hydrogel, acquired this capacity in the concomitant presence of type I or III collagens. Both types of ECM compound, HA and collagens, possess the capacity to stimulate production of metalloprotease-2, recognized otherwise as a factor for poor cancer prognosis. HA-provoked cellular invasiveness resulted from CD44-mediated increase in cytosolic [Ca2+] and its subsequent hydrolysis due to ADAM (a disintegrin and metalloprotease) proteolytic activity. Interestingly, this mechanism seemed to be absent in non-invasive cancer cell lines. Conclusion: Furthermore, using basic fibroblast growth factor and stromal cell-derived factor-1,, we also show that this three-dimensional reticulate matrix may be considered as a valuable model to study chemokinetic and chemotactic potentials of factors present in tumour stroma. [source] | |||||||||||||