scholarly journals Brain-derived neurotrophic factor regulates cell motility in human colon cancer

2015 ◽  
Vol 22 (3) ◽  
pp. 455-464 ◽  
Author(s):  
Ssu-Ming Huang ◽  
Chingju Lin ◽  
Hsiao-Yun Lin ◽  
Chien-Ming Chiu ◽  
Chia-Wei Fang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Neurotrophic Factor ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Colon Cancer Cell ◽  
Cancer Cell Migration ◽  
Colon Cancer Cells

Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to affect cancer cell metastasis and migration. In the present study, we investigated the mechanisms of BDNF-induced cell migration in colon cancer cells. The migratory activities of two colon cancer cell lines, HCT116 and SW480, were found to be increased in the presence of human BDNF. Heme oxygenase-1 (HO)-1 is known to be involved in the development and progression of tumors. However, the molecular mechanisms that underlie HO-1 in the regulation of colon cancer cell migration remain unclear. Expression of HO-1 protein and mRNA increased in response to BDNF stimulation. The BDNF-induced increase in cell migration was antagonized by a HO-1 inhibitor and HO-1 siRNA. Furthermore, the expression of vascular endothelial growth factor (VEGF) also increased in response to BDNF stimulation, as did VEGF mRNA expression and transcriptional activity. The increase in BDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Moreover, transfection with HO-1 siRNA effectively reduced the increased VEGF expression induced by BDNF. The BDNF-induced cell migration was regulated by the ERK, p38, and Akt signaling pathways. Furthermore, BDNF-increased HO-1 and VEGF promoter transcriptional activity were inhibited by ERK, p38, and AKT pharmacological inhibitors and dominant-negative mutants in colon cancer cells. These results indicate that BDNF increases the migration of colon cancer cells by regulating VEGF/HO-1 activation through the ERK, p38, and PI3K/Akt signaling pathways. The results of this study may provide a relevant contribution to our understanding of the molecular mechanisms by which BDNF promotes colon cancer cell motility.

scholarly journals GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

2013 ◽  
Vol 21 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Ssu-Ming Huang ◽  
Tzu-Sheng Chen ◽  
Chien-Ming Chiu ◽  
Leang-Kai Chang ◽  
Kuan-Fu Liao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Transcriptional Activity ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Cancer Cell Migration ◽  
Colon Cancer Cells ◽  
Human Colon Cancer

Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, has been shown to affect cancer cell metastasis and invasion. However, the molecular mechanisms underlying GDNF-induced colon cancer cell migration remain unclear. GDNF is found to be positively correlated with malignancy in human colon cancer patients. The migratory activities of two human colon cancer cell lines, HCT116 and SW480, were found to be enhanced in the presence of human GDNF. The expression of vascular endothelial growth factor (VEGF) was also increased in response to GDNF stimulation, along with VEGF mRNA expression and transcriptional activity. The enhancement of GDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Our results also showed that the expression of VEGF receptor 1 (VEGFR1) was increased in response to GDNF stimulation, whereas GDNF-induced cancer cell migration was reduced by a VEGFR inhibitor. The GDNF-induced VEGF expression was regulated by the p38 and PI3K/Akt signaling pathways. Treatment with GDNF increased nuclear hypoxia-inducible factor 1 α (HIF1α) accumulation and its transcriptional activity in a time-dependent manner. Moreover, GDNF increased hypoxia responsive element (HRE)-containing VEGF promoter transcriptional activity but not that of the HRE-deletion VEGF promoter construct. Inhibition of HIF1α by a pharmacological inhibitor or dominant-negative mutant reduced the GDNF-induced migratory activity in human colon cancer cells. These results indicate that GDNF enhances the migration of colon cancer cells by increasing VEGF–VEGFR interaction, which is mainly regulated by the p38, PI3K/Akt, and HIF1α signaling pathways.

scholarly journals Postcolectomy Peritoneal Environment Increases Colon Cancer Cell Migration Capacity

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Liron Berkovich ◽  
Ronen Ghinea ◽  
Salem Majdop ◽  
Baruch Shpitz ◽  
Ian White ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colorectal Resection ◽  
Colon Cancer Cell ◽  
Cancer Cell Migration ◽  
Colon Cancer Cells ◽  
Migration Capacity

Background.Clinical data and animal models support an association between postoperative inflammatory response and the risk of colorectal cancer recurrence. Our aim was to evaluate postoperative peritoneal inflammation and its impact on cultured colon cancer cells’ migration capacity.Methods.23 patients undergoing elective colorectal resection with uneventful recovery were prospectively enrolled. Patients were operated on for both malignant and benign etiologies. Peritoneal fluids collected at surgery initiation and after surgery were evaluated for their effect on migration potential of human colon cancer cells using anin vitroscratch assay and on TNF-α, IL-1β, IL-6, and IL-10 levels using bead-based fluorokine-linked multianalyte profiling.Results.Postoperative peritoneal fluid from all patients increased the migration capacity of colon cancer cells compared to preoperative levels. This effect was significant during the first two postoperative days and decreased thereafter. The increase in colon cancer cell migration capacity correlated with increased levels of peritoneal TNF-αand IL-10.Conclusion.In this pilot study, we have demonstrated that the intraperitoneal environment following colorectal resection significantly enhances colon cancer cells migration capacity. This effect is associated with postoperative intra-abdominal cytokines level. A larger scale study in colorectal cancer patients is needed in order to correlate these findings with perioperative parameters and clinical outcome.

scholarly journals MicroRNA-340-5p inhibits colon cancer cell migration via targeting of RhoA

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anwar Algaber ◽  
Amr Al-Haidari ◽  
Raed Madhi ◽  
Milladur Rahman ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Colon Cancer Cells ◽  
Cell Migration And Invasion ◽  
Ht 29

Abstract Colon cancer is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the most insidious aspect of cancer progression. Convincing data suggest that microRNAs (miRs) play a key function in colon cancer biology. We examined the role of miR-340-5p in regulating RhoA expression as well as cell migration and invasion in colon cancer cells. Levels of miR-340-5p and RhoA mRNA varied inversely in serum-free and serum-grown HT-29 and AZ-97 colon cancer cells. It was found transfection with miR-340-5p not only decreased expression of RhoA mRNA and protein levels in HT-29 cells but also reduced colon cancer cell migration and invasion. Bioinformatics analysis predicted one putative binding sites at the 3′-UTR of RhoA mRNA. Targeting this binding site with a specific blocker reversed mimic miR-340-5p-induced inhibition of RhoA activation and colon cancer cell migration and invasion. These novel results suggest that miR-340-5p is an important regulator of colon cancer cell motility via targeting of RhoA and further experiments are warranted to evaluate the role of miR-340-5p in colon cancer metastasis.

scholarly journals CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells

2021 ◽  
Author(s):  
Mattias Lepsenyi ◽  
Nader Algethami ◽  
Amr A. Al-Haidari ◽  
Anwar Algaber ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Cancer Cell Adhesion ◽  
And Migration ◽  
Cxcr2 Antagonist

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.

Akt pathway is involved in colon cancer cell migration

2010 ◽  
Vol 36 (11) ◽  
pp. 1128-1129
Author(s):  
Anur Miah ◽  
S. Yang ◽  
M. Winslet
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Akt Pathway ◽  
Cancer Cell Migration

scholarly journals Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases

2010 ◽  
Vol 102 (4) ◽  
pp. 774-782 ◽  
Author(s):  
T Ishiguro ◽  
H Avila ◽  
S-Y Lin ◽  
T Nakamura ◽  
M Yamamoto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Chloride Channel ◽  
Colon Cancer Cell ◽  
Cancer Cell Migration ◽  
Gene Trapping

scholarly journals A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 328
Author(s):  
Yihe Zhang ◽  
Bingjie Jiang ◽  
Meng Huee Lee
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Physical Contact ◽  
Physical Interaction ◽  
Matrix Remodeling ◽  
Cancer Cell Migration ◽  
Cell Type

Stromal fibroblasts surrounding cancer cells are a major and important constituent of the tumor microenvironment not least because they contain cancer-associated fibroblasts, a unique fibroblastic cell type that promotes tumorigenicity through extracellular matrix remodeling and secretion of soluble factors that stimulate cell differentiation and invasion. Despite much progress made in understanding the molecular mechanisms that underpin fibroblast–tumor cross-talk, relatively little is known about the way the two cell types interact from a physical contact perspective. In this study, we report a novel three-dimensional dumbbell model that would allow the physical interaction between the fibroblasts and cancer cells to be visualized and monitored by microscopy. To achieve the effect, the fibroblasts and cancer cells in 50% Matrigel suspension were seeded as independent droplets in separation from each other. To allow for cell migration and interaction, a narrow passage of Matrigel causeway was constructed in between the droplets, effectively molding the gel into the shape of a dumbbell. Under time-lapse microscopy, we were able to visualize and image the entire process of fibroblast-guided cancer cell migration event, from initial vessel-like structure formation by the fibroblasts to their subsequent invasion across the causeway, attracting and trapping the cancer cells in the process. Upon prolonged culture, the entire population of fibroblasts eventually infiltrated across the passage and condensed into a spheroid-like cell mass, encapsulating the bulk of the cancer cell population within. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction.

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