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Migratory Potential (migratory + potential)
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] The green tea compound, (,)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Kimberly M. Rieger-Christ Abstract Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (,)-epigallocatechin gallate (EGCG,the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC50 range of 70,87 µM. At a concentration of 20 µM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P,,,0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. J. Cell. Biochem. 102: 377,388, 2007. © 2007 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 ActivityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Melissa J. Mulla Citation Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010 Problem Women with antiphospholipid antibodies (aPL) are at risk of recurrent miscarriage and pre-eclampsia. aPL target the placenta by binding to ,2 -glycoprotein I (,2 GPI) expressed by the trophoblast. The objective of this study was to evaluate if and how aPL affect first trimester trophoblast migration. Method of study First trimester trophoblast cells were treated with anti-,2 GPI monoclonal antibodies. Migration was determined using a two-chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme-linked immunosorbent assay, and signal transducer and activator of transcription 3 (STAT3) activation was assessed by western blot. Results Trophoblast cells constitutively secreted IL-6 in a time-dependent manner and this directly correlated with STAT3 phosphorylation. In the presence of anti-,2 GPI Abs, trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like receptor 4/MyD88-independent manner and this correlated with a reduction in phosphorylated STAT3 levels. In addition, the anti-,2 GPI Abs reduced the migratory potential of trophoblast. Heparin was able to reverse aPL-dependent inhibition of trophoblast IL-6 secretion and migration. Conclusion This study demonstrates that aPL limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent these effects, our findings may explain why women with antiphospholipid syndrome, treated with heparin, remain at risk of developing obstetrical syndromes, associated with impaired deep placentation, such as pre-eclampsia. [source] Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell lineTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006William J. Brackenbury We have shown previously that voltage-gated Na+ channels (VGSCs) are up-regulated in human metastatic disease (prostate, breast and small-cell lung cancers), and that VGSC activity potentiates metastatic cell behaviours. However, the mechanism(s) regulating functional VGSC expression in cancer cells remains unknown. We investigated the possibility of activity-dependent (auto)regulation of VGSC functional expression in the strongly metastatic Mat-LyLu model of rat prostate cancer. Pretreatment with tetrodotoxin (TTX) for 24,72 h subsequently suppressed peak VGSC current density without affecting voltage dependence. The hypothesis was tested that the VGSC auto-regulation occurred via VGSC-mediated Na+ influx and subsequent activation of protein kinase A (PKA). Indeed, TTX pretreatment reduced the level of phosphorylated PKA, and the PKA inhibitor KT5720 decreased, whilst the adenylate cyclase activator forskolin and the Na+ ionophore monensin both increased the peak VGSC current density. TTX reduced the mRNA level of Nav1.7, predominant in these cells, and VGSC protein expression at the plasma membrane, although the total VGSC protein level remained unchanged. TTX pretreatment eliminated the VGSC-dependent component of the cells' migration in Transwell assays. We concluded that the VGSC activity in Mat-LyLu rat prostate cancer cells was up-regulated in steady-state via a positive feedback mechanism involving PKA, and this enhanced the cells' migratory potential. [source] | |||||||||||||