scholarly journals Enhanced nitric oxide signaling amplifies vasorelaxation of human colon cancer feed arteries

2019 ◽  
Vol 316 (1) ◽  
pp. H245-H254 ◽  
Author(s):  
Ninna C. S. Voss ◽  
Henrik Kold-Petersen ◽  
Ebbe Boedtkjer
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Human Colon ◽  
No Synthase ◽  
Cancer Tissue ◽  
Solid Cancer ◽  
Tumor Perfusion ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Feed Arteries

Inadequate perfusion of solid cancer tissue results in low local nutrient and oxygen levels and accumulation of acidic waste products. Previous investigations have focused primarily on tumor blood vessel architecture, and we lack information concerning functional differences between arteries that deliver blood to solid cancer tissue versus normal tissue. Here, we use isometric myography to study resistance-sized arteries from human primary colon adenocarcinomas and matched normal colon tissue. Vasocontraction of colon cancer feed arteries in response to endothelin-1 and thromboxane stimulation is attenuated compared with normal colon arteries despite similar wall dimensions and comparable contractions to arginine vasopressin and K+-induced depolarization. Acetylcholine-induced vasorelaxation and endothelial NO synthase expression are increased in colon cancer feed arteries compared with normal colon arteries, whereas vasorelaxation to exogenous NO donors is unaffected. In congruence, the differences in vasorelaxant and vasocontractile function between colon cancer feed arteries and normal colon arteries decrease after NO synthase inhibition. Rhythmic oscillations in vascular tone, known as vasomotion, are of lower amplitude but similar frequency in colon cancer feed arteries compared with normal colon arteries. In conclusion, higher NO synthase expression and elevated NO signaling amplify vasorelaxation and attenuate vasocontraction of human colon cancer feed arteries. We propose that enhanced endothelial function augments tumor perfusion and represents a potential therapeutic target. NEW & NOTEWORTHY Local vascular resistance influences tumor perfusion. Arteries supplying human colonic adenocarcinomas show enhanced vasorelaxation and reduced vasocontraction mainly due to elevated nitric oxide-mediated signaling. Rhythmic oscillations in tone, known as vasomotion, are attenuated in colon cancer feed arteries.

scholarly journals Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Ninna C. S. Voss ◽  
Henrik Kold-Petersen ◽  
Mikkel B. Henningsen ◽  
Casper Homilius ◽  
Ebbe Boedtkjer
Keyword(s):  
Colon Cancer ◽  
Steady State ◽  
Intracellular Ph ◽  
Human Colon ◽  
Cancer Tissue ◽  
Normal Colon ◽  
Colon Tissue ◽  
Colon Cancer Tissue ◽  
Human Colon Cancer ◽  
Acid Extrusion

Increased metabolism accelerates local acid production in cancer tissue. The mechanisms eliminating acidic waste products from human colon cancer tissue represent promising therapeutic targets for pharmacological manipulation in order to improve prognosis for the increasing number of patients with colon cancer. We sampled biopsies of human colonic adenocarcinomas and matched normal colon tissue from patients undergoing colon cancer surgery. We measured steady-state intracellular pH and rates of net acid extrusion in freshly isolated human colonic crypts based on fluorescence microscopy. Net acid extrusion was almost entirely (>95%) Na+-dependent. The capacity for net acid extrusion was increased and steady-state intracellular pH elevated around 0.5 in crypts from colon cancer tissue compared with normal colon tissue irrespective of whether they were investigated in the presence or absence of CO2/HCO3–. The accelerated net acid extrusion from the human colon cancer tissue was sensitive to the Na+/H+-exchange inhibitor cariporide. We conclude that enhanced net acid extrusion via Na+/H+-exchange elevates intracellular pH in human colon cancer tissue.

Expression of inducible nitric Oxide synthase(INOS) in human colon cancer tissue

2000 ◽  
Vol 118 (4) ◽  
pp. A1392
Author(s):  
Jeong Wook Kim ◽  
Seoung Hyeock Han ◽  
Hyun Joo Jeong ◽  
Jae Hyuk Do ◽  
Sae Kyung Chang
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Human Colon ◽  
Cancer Tissue ◽  
Colon Cancer Tissue ◽  
Human Colon Cancer ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Expression of Gelatinase-A (MMP-2) in Human Colon Cancer and Normal Colon Mucosa

Tumor Biology ◽  
2001 ◽  
Vol 22 (6) ◽  
pp. 383-389 ◽  
Author(s):  
S. Papadopoulou ◽  
A. Scorilas ◽  
N. Arnogianaki ◽  
B. Papapanayiotou ◽  
A. Tzimogiani ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Gelatinase A ◽  
Colon Mucosa ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Normal Colon Mucosa

A metastatic model of human colon cancer constructed using cecal implantation of cancer tissue in nude mice

Surgery Today ◽  
1993 ◽  
Vol 23 (5) ◽  
pp. 420-423 ◽  
Author(s):  
Toshiharu Furukawa ◽  
Tetsuro Kubota ◽  
Masahiko Watanabe ◽  
Tsong-Hong Kuo ◽  
Hideki Nishibori ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Nude Mice ◽  
Human Colon ◽  
Cancer Tissue ◽  
Human Colon Cancer

Influence of the nitric oxide donor glyceryl trinitrate on apoptotic pathways in human colon cancer cells

2002 ◽  
Vol 123 (1) ◽  
pp. 235-246 ◽  
Author(s):  
Anne Millet ◽  
Ali Bettaieb ◽  
Flore Renaud ◽  
Laurent Prevotat ◽  
Arlette Hammann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Glyceryl Trinitrate ◽  
Cancer Cells ◽  
Human Colon ◽  
Nitric Oxide Donor ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Apoptotic Pathways ◽  
Human Colon Cancer Cells

scholarly journals cis-Golgi resident proteins and O-glycans are abnormally compartmentalized in the RER of colon cancer cells

1993 ◽  
Vol 105 (3) ◽  
pp. 819-830 ◽  
Author(s):  
G. Egea ◽  
C. Franci ◽  
G. Gambus ◽  
T. Lesuffleur ◽  
A. Zweibaum ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Golgi Apparatus ◽  
Cancer Cells ◽  
Neoplastic Transformation ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Protein Disulphide Isomerase ◽  
Cancer Tissues

Neoplastic transformation is commonly associated with altered glycosylation of proteins and lipids. To understand the basis for altered mucin glycosylation, we have examined the distribution of RER markers, a cis-Golgi resident protein, and the GalNAc alpha-O-Ser/Thr epitope (Tn) in human colon cancer cells and in normal colon. In cultured mucin-producing colon cancer cells, Gal-NAc alpha-O-Ser/Thr was found in mucin droplets and in RER cisternae. In addition, the Golgi apparatus was disorganized in a proportion of cells and a 130 kDa cis-Golgi resident protein was also abnormally redistributed to the RER. The distribution of the MUC2 intestinal apomucin, protein disulphide isomerase, Gal-NAc alpha-O-Ser/Thr, and the 130 kDa cis-Golgi resident protein was analysed in normal colon and in colon cancer tissues. In normal colon, MUC2 apomucin and protein disulphide isomerase were located in the RER, whereas the cis-Golgi resident protein and GalNAc alpha-O-Ser/Thr were detected only in the cis-Golgi compartment. In contrast, the two Golgi markers colocalized with the MUC2 apomucin and protein disulphide isomerase in the RER of colon cancer cells. On the basis of these results, we propose that in colon cancer cells a redistribution of molecules normally present in the Golgi apparatus takes place; this alteration may contribute to the abnormal glycosylation of proteins and lipids associated with neoplastic transformation.

scholarly journals CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties

2021 ◽  
Vol 9 ◽  
Author(s):  
Shudong Zhu ◽  
Yan Zhu ◽  
Qiuwen Wang ◽  
Yi Zhang ◽  
Xialing Guo
Keyword(s):  
Dna Methylation ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Dna Methyltransferases ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Matrigel Invasion

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.

scholarly journals The LIM Protein Ajuba Augments Tumor Metastasis in Colon Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1913
Author(s):  
Noëlle Dommann ◽  
Daniel Sánchez-Taltavull ◽  
Linda Eggs ◽  
Fabienne Birrer ◽  
Tess Brodie ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Human Colon ◽  
Tumor Burden ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Potential Candidate ◽  
Sequencing Data ◽  
Human Colon Cancer ◽  
Cancer Genome Atlas

Colorectal cancer, along with its high potential for recurrence and metastasis, is a major health burden. Uncovering proteins and pathways required for tumor cell growth is necessary for the development of novel targeted therapies. Ajuba is a member of the LIM domain family of proteins whose expression is positively associated with numerous cancers. Our data shows that Ajuba is highly expressed in human colon cancer tissue and cell lines. Publicly available data from The Cancer Genome Atlas shows a negative correlation between survival and Ajuba expression in patients with colon cancer. To investigate its function, we transduced SW480 human colon cancer cells, with lentiviral constructs to knockdown or overexpress Ajuba protein. The transcriptome of the modified cell lines was analyzed by RNA sequencing. Among the pathways enriched in the differentially expressed genes, were cell proliferation, migration and differentiation. We confirmed our sequencing data with biological assays; cells depleted of Ajuba were less proliferative, more sensitive to irradiation, migrated less and were less efficient in colony formation. In addition, loss of Ajuba expression decreased the tumor burden in a murine model of colorectal metastasis to the liver. Taken together, our data supports that Ajuba promotes colon cancer growth, migration and metastasis and therefore is a potential candidate for targeted therapy.

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