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 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.

Incomplete processing of progastrin expressed by human colon cancer cells: role of noncarboxyamidated gastrins

1994 ◽  
Vol 266 (3) ◽  
pp. G459-G468 ◽  
Author(s):  
P. Singh ◽  
Z. Xu ◽  
B. Dai ◽  
S. Rajaraman ◽  
N. Rubin ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Colon ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Colon Cancer Cell Lines

Gastrin is mitogenic for several colon cancers. To assess a possible autocrine role of gastrin in colon cancers, we examined human colon cancer cell lines for expression of gastrin mRNA and various forms of gastrin. Gastrin mRNA was not detected in the majority of colon cancer cell lines by Northern hybridization but was detected in all human colon cancer lines by the sensitive method of reverse transcriptase-polymerase chain reaction (PCR). Gastrin mRNA was quantitated by the competitive PCR method. The majority of cell lines expressed very low levels of gastrin mRNA (< 1-5 copies/cell); only one cell line expressed > 20 copies/cell. The mature carboxyamidated form of gastrin was not detected in any of the cell lines by radioimmunoassay or immunocytochemistry. Results suggested that either gastrin mRNA expressed by colon cancer cells was altered (mutated) or posttranslational processing of progastrin was incomplete. Gastrin cDNA from all the colon cancer cell lines had an identical sequence to the published sequence of human gastrin cDNA. Specific antibodies against precursor forms of gastrin were used, and significant concentrations of nonamidated (glycine-extended) and prepro forms of gastrin were measured in tumor extracts of representative colon cancer cell lines. The presence of precursor forms of gastrin suggested a lack of one or more of the processing enzymes and/or cofactors. Significant concentrations of the processing enzyme (peptidylglycine alpha-amidating monooxygenase) were detected in colon cancer cells by immunocytochemistry. Therefore, lack of other cofactors or enzymes may be contributing to incomplete processing of precursor forms of gastrin, which merits further investigation. Since low levels of gastrin mRNA were expressed by the majority of human colon cancer cell lines and progastrin was incompletely processed, it seems unlikely that gastrin can function as a viable autocrine growth factor for colon cancer cells. High concentrations of glycine-extended gastrin-17 (GG) (> 10(-6) M) were mitogenic for a gastrin-responsive human colon cancer (DLD-1) cell line in vitro. It remains to be seen if GG or other precursor forms of gastrin are similarly mitogenic in vivo, which may then lend credibility to a possible autocrine role of gastrinlike peptides in colon cancers.

scholarly journals Wnt5a promotes human colon cancer cell migration and invasion but does not augment intestinal tumorigenesis in Apc 1638N mice

2013 ◽  
Vol 34 (11) ◽  
pp. 2629-2638 ◽  
Author(s):  
Elvira R.M. Bakker ◽  
Asha Mooppilmadham Das ◽  
Werner Helvensteijn ◽  
Patrick F. Franken ◽  
Sigrid Swagemakers ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Human Colon Cancer Cell ◽  
Human Colon Cancer ◽  
Intestinal Tumorigenesis

scholarly journals PRMT1 inhibition induces differentiation of colon cancer cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander Plotnikov ◽  
Noga Kozer ◽  
Galit Cohen ◽  
Silvia Carvalho ◽  
Shirly Duberstein ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Differentiation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Differentiation Therapy ◽  
Human Colon Cancer ◽  
Ht 29

AbstractDifferentiation therapy has been recently revisited as a prospective approach in cancer therapy by targeting the aberrant growth, and repairing the differentiation and cell death programs of cancer cells. However, differentiation therapy of solid tumors is a challenging issue and progress in this field is limited. We performed High Throughput Screening (HTS) using a novel dual multiplex assay to discover compounds, which induce differentiation of human colon cancer cells. Here we show that the protein arginine methyl transferase (PRMT) type 1 inhibitor, MS023, is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Differentiation changes in the highly aggressive human colon cancer cell line (HT-29) were proved by proteomic and genomic approaches. Growth of HT-29 xenograft in nude mice was significantly delayed upon MS023 treatment and immunohistochemistry of tumor indicated differentiation changes. These findings may lead to development of clinically effective anti-cancer drugs based on the mechanism of cancer cell differentiation.

scholarly journals Trolox induces inhibition of cell proliferation and apoptosis in human colon cancer cells

2015 ◽  
Vol 10 (4) ◽  
pp. 931 ◽  
Author(s):  
Li-Guang Yang ◽  
Xiang-An Tian ◽  
Xiao-Yan Li ◽  
Jian-Guo Huang ◽  
Nai-Qing Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Colon Cancer Cell Lines

<p class="Abstract">In the present study, the effect of trolox on human colon cancer cell lines was investigated. The results revealed that trolox treatment caused inhibition of cell growth in T84 and HCT-15 colon cancer cell lines in a dose-dependent manner. The inhibition was significant at 50 µM of trolox after 48 hours in both cell lines. Trolox treatment promoted expression of p38 and inhibited expression of survivin and Akt. It also induced cleavage of PARP and caspase-3 and ultimately induced apoptosis in T84 and HCT-15 cells. The tumor growth was inhibited significantly in the xenotransplanted mice on treatment with trolox compared to the control group. Since trolox treatment exhibits inhibitory effect on the proliferation of colon cancer cells and inhibits tumor growth in vivo therefore, can be of therapeutic importance for the treatment of colon cancer.</p><p> </p>

scholarly journals The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3798
Author(s):  
Nor Isnida Ismail ◽  
Iekhsan Othman ◽  
Faridah Abas ◽  
Nordin H. Lajis ◽  
Rakesh Naidu
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Curcumin Analogue ◽  
Human Colon Cancer Cells

The cytotoxic and apoptotic effects of turmeric (Curcuma longa) on colon cancer have been well documented but specific structural modifications of curcumin have been shown to possess greater growth-suppressive potential on colon cancer than curcumin. Therefore, the aim of this study is to identify the anti-cancer properties of curcumin analogue-MS13, a diarylpentanoid on the cytotoxicity, anti-proliferative and apoptotic activity of primary (SW480) and metastatic (SW620) human colon cancer cells. A cell viability assay showed that MS13 has greater cytotoxicity effect on SW480 (EC50: 7.5 ± 2.8 µM) and SW620 (EC50: 5.7 ± 2.4 µM) compared to curcumin (SW480, EC50: 30.6 ± 1.4 µM) and SW620, EC50: 26.8 ± 2.1 µM). Treatment with MS13 at two different doses 1X EC50 and 2X EC50 suppressed the colon cancer cells growth with lower cytotoxicity against normal cells. A greater anti-proliferative effect was also observed in MS13 treated colon cancer cells compared to curcumin at 48 and 72 h. Subsequent analysis on the induction of apoptosis showed that MS13 treated cells exhibited morphological features associated with apoptosis. The findings are also consistent with cellular apoptotic activities shown by increased caspase-3 activity and decreased Bcl-2 protein level in both colon cancer cell lines. In conclusion, MS13 able to suppress colon cancer cell growth by inhibiting cell proliferation and induce apoptosis in primary and metastatic human colon cancer cells.

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.

Effect of 5-fluorouracil on membranous PD-L1 expression in colon cancer cells.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 592-592 ◽  
Author(s):  
Gaurav Goel ◽  
Krishnaveni Ramanan ◽  
Christof Kaltenmeier ◽  
Lin Zhang ◽  
Gordon J. Freeman ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Colon ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Colon Cancer Cell Lines

592 Background: Colorectal cancer (CRC) is a major public health problem worldwide. Chemotherapy consisting of a fluoropyrimidine backbone constitutes a major therapeutic modality used in the treatment of CRC patients. However, cancer cells often develop resistance to such cytotoxic chemotherapy and this represents a major therapeutic challenge. B7-homolog 1 (B7-H1), also known as programmed death ligand-1 (PD-L1) is an immunoregulatory protein that belongs to the B7 family of T-cell co-regulatory molecules, and is overexpressed in several human tumors. Upregulation of PD-L1 expression is an important mechanism by which tumor cells can escape host T-cell immunity. Emerging evidence suggests that chemotherapeutic agents can regulate PD-L1 expression on cancer cells, which may have an impact on anti-tumor immunity and immune evasion. We performed this study to evaluate the effect of 5-Fluorouracil (5-FU) on PD-L1 expression in colon cancer cell lines, using an in vitro approach. Methods: Flow cytometry and western immunoblot analyses for PD-L1 expression were performed on human colon cancer cell lines (HCT116-WT, HCT116-p53 KO, SW480, HT29) upon treatment with IFN-ɣ and 5-FU. Results: We found that the tested human colon cancer cell lines rarely expressed PD-L1 protein on their cell surface at baseline, but a high level of expression was induced by treatment with IFN-ɣ. More importantly, we demonstrated that the chemotherapeutic agent 5-FU induces PD-L1 expression in colon cancer cells. Conclusions: It is therefore plausible that combining 5-FU with PD-1/PD-L1 blockade might help overcome some of the chemoresistance to 5-FU and thereby enhance its anti-cancer activity. Further experiments are being planned to formally test this hypothesis.

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