The myeloid cell biomarker EMR1 is ectopically expressed in colon cancer

OBJECTIVE: The microenvironment of colon cancer (CC) is heterogeneous including cells of myeloid lineage affecting tumor growth and metastasis. Two functional subtypes of myeloid cells have been identified; one (M1) is tumor-inhibitory and the other one (M2) is tumor-promoting. Whether the three myeloid markers EMR1, CD206 and CD86 are expressed only in the infiltrating myeloid cells or also in the tumor cells was investigated. METHODS: Expression of the myeloid markers was investigated in CC at the mRNA and protein levels in primary tumors and lymph nodes. mRNA expression was also determined in 5 CC cell lines. Protein expression was investigated by two-color immunofluorescence and consecutive-sections-immune-staining combined with morphometry using specific antibodies for the myeloid cell markers and the epithelial cell markers CEACAM5 and EpCAM. RESULTS: EMR1 and CD86, but not CD206, mRNA levels were significantly higher in CC primary tumors compared to apparently normal colon tissue (P < 0.0001). EMR1 mRNA levels were significantly higher in both hematoxylin-eosin positive (H&E(+)) and H&E(–) lymph nodes of CC patients compared to control nodes (P = 0.03 and P = 0.01, respectively). EMR1 and CD206 mRNAs were expressed in 4/5 and 5/5 CC cell lines, respectively, while CD86 mRNA was not expressed. Immuno-morphometry revealed that about 20% of the tumor cells expressed EMR1 and CD206. Positive cells were tumor cells as revealed by anti-CEACAM5 and anti-EpCAM staining. The number of EMR1, CD206 and CD86 positive cells were significantly increased in CC primary tumors compared to normal colon tissue (P < 0.0001). However, CD206 was also expressed in normal colonocytes. Only EMR1 showed significantly increased numbers of positive tumor cells in H&E(+) nodes compared to H&E(-) nodes (P = 0.001). EMR1 expression in CC tumor cells correlated with CXCL17 expressing tumor cells. CONCLUSION: EMR1, like the chemokine CXCL17, is ectopically expressed in colon cancer possibly in the same cancer cells.

Download Full-text

The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome

International Journal of Molecular Sciences ◽

10.3390/ijms20225793 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5793 ◽

Cited By ~ 3

Author(s):

Manar AbdelMageed ◽

Haytham Ali ◽

Lina Olsson ◽

Gudrun Lindmark ◽

Marie-Louise Hammarström ◽

...

Keyword(s):

Colon Cancer ◽

Protein Expression ◽

Lymph Nodes ◽

Cancer Patients ◽

Mrna Levels ◽

Colon Tissue ◽

Regional Lymph Nodes ◽

Primary Tumors ◽

Kaplan Meier ◽

Cancer Outcome

Chemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

Download Full-text

Immunihistochemical detection of galNAc-T6 to predict survival in patients with colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14682 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14682-e14682

Author(s):

Luis Ubillos ◽

Mariela Rondan ◽

Edgardo Berriel ◽

Daniel Mazal ◽

Enrique Barrios ◽

...

Keyword(s):

Colon Cancer ◽

Prognostic Marker ◽

Cell Lines ◽

Initial Step ◽

Cancer Tissue ◽

Normal Colon ◽

Colon Tissue ◽

Tissue Samples ◽

Independent Prognostic Marker ◽

Colon Cell

e14682 Background: Alterations in the O-glycosylation is one of the most common changes during colon carcinogenesis, which leads to the expression of short O-glycan antigens (Tn, sialyl-Tn, Tk, and core 6). These structures are associated with malignant behavior being actively investigated as targets for immunotherapy. The enzymes of GalNAc-T family regulate the initial step in mucins O-glycosylation and could be responsible for the altered glycosylation observed in cancer. The aim of this work was to evaluate the expression of GalNAc-T6 in colon cancer, and to determine its role as prognostic marker. Methods: We evaluated GalNAc-T6 expression in colon cell lines by immunocytochemistry, and in colon cancer tissue samples by immunohistochemistry using the monoclonal antibody T6.3 developed by us (Berois et al. J Histochem Cytochem. 2006). We analyzed 103 colon cancer samples and 10 normal colon tissues. Results: We found that GalNAc-T6 (usually expressed in normal placenta, trachea, pancreas and brain) is detected in colon cancer cell lines. GalNAc-T6 was also detected by immunohistochemistry in 50.5% of samples with cancer and no expression was found in normal colon tissue. The staining pattern was predominantly cytoplasmic. Multivariate analysis showed that GalNAc-T6 expression is an independent prognostic marker predicting improved survival in patients with positive tumors (p 0.014). Conclusions: GalNAc-T6 could be a new independent prognostic marker to predict better outcome in colon cancer patients.

Download Full-text

BNIP3L (Nix) expression in colon cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15097 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15097-e15097

Author(s):

J. E. Littlejohn ◽

D. Jupiter ◽

X. Cao ◽

L. Zhang ◽

M. Shabahang ◽

...

Keyword(s):

Colon Cancer ◽

Human Colon ◽

Mrna Levels ◽

Normal Colon ◽

Colon Tissue ◽

Human Colon Cancer ◽

Variable Expression ◽

Colon Tumors ◽

Normal Colon Tissue ◽

Protein Levels

e15097 Background: Microenvironmental adaptation to hypoxic conditions is critical for a cell to survive in a growing solid tumor. BNIP3L (Nix) mediates apoptosis during hypoxia in cancer cell lines, and Nix knockdown promotes tumor growth in-vivo through decreased apoptosis and increased proliferation, suggesting a means by which cells can adapt. Little is known specifically about Nix expression and its importance in human colon cancer. To gain insight into expression of this gene in colon tumors, the present study analyzed mRNA microarray data from 227 colon tumors and 22 normal colon tissue samples and queried differential expression of Nix. These results were compared to the protein levels present in human colon tumors. Methods: mRNA expression of 227 human colon tumors (made available by the Expression Project for Oncology (expO)) and 22 normal colon samples (retrieved from the Gene Expression Omnibus (GEO)) was analyzed. These samples were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array, assaying 17,726 NCBI Entrez genes. Immunohistochemistry was performed on human tissue microarray CO701 (US Biomax, Inc.) containing 62 tumor samples. Results: Nix mRNA levels were shown to increase from normal to cancer (log-fold change of 0.961, Benjamini-Hochberg FDR adjusted p < 0.001). IHC demonstrated variable levels of Nix present in colon tumors: 38/62 (61.3%) of tumors stained positive for Nix while 24/62 (38.7%) were negative. Conclusions: We have shown that mRNA levels of Nix are upregulated in the transition from normal colon tissue to cancer but that protein levels in tumors demonstrate variable expression. This suggests that silencing of Nix occurs at various stages of tumorigenic progression and results in isolated populations of cells within a growing tumor that are uniquely resistant to apoptosis. Better understanding of Nix in the context of a growing colon tumor is needed and could lead to development of more successful therapeutics. No significant financial relationships to disclose.

Download Full-text

Phosphodiesterase 10, a novel target in colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.503 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 503-503

Author(s):

Suzanne Russo ◽

Nan Li ◽

Kevin Lee ◽

Yaguang Xi ◽

Bing Zhu ◽

...

Keyword(s):

Colon Cancer ◽

Mouse Model ◽

Tumor Cell ◽

Tumor Cells ◽

Cell Lines ◽

Human Tumor ◽

Clinical Samples ◽

Mrna Levels ◽

Tumor Cell Lines ◽

Sirna Knockdown

503 Background: Elevation of intracellular cGMP is known to inhibit tumor proliferation and induce apoptosis, although the phosphodiesterase (PDE) isozymes that regulate cGMP levels in tumor cells have not been well studied. We report first evidence that PDE10 is elevated in colon tumors compared with normal colon and suggest that PDE10 inhibitors can be used for the treatment or prevention of colon cancer. Methods: PDE10 protein and mRNA levels were measured in human colon tumor cells (HT29, HCT116, SW480, Caco2), normal colonocytes (NCM460), human clinical samples, and ApcMin/+ mouse model. Two chemically distinct PDE10 selective inhibitors, PQ-10 and Pf-2545920, were tested against the cell lines. The NCI-60 panel of human tumor cell lines was also screened against Pf-2545920 to identify potential differences in sensitivity among histologically diverse tumor types. We also performed siRNA knockdown studies in colonocytes and tumor cell lines. To determine the effect of the PDE10 siRNA knockdown on cyclic nucleotide hydrolysis, whole cell lysates from transfected cells were assayed for PDE activity using cGMP or cAMP as substrates. Results: PDE10 levels were low in normal colonocytes (NCM460) and elevated in tumor cell lines. Similarly, PDE10 was elevated human clinical specimens and the ApcMin+/ mouse model compared with normal mucosa. PDE10 inhibitors and siRNA selectively inhibited colonic tumor growth while stable knockdown inhibited colony formation and increased doubling time. Pf-2545920 also supressed growth of all cell lines within the NCI-60 panel. In comparison with lysates from vector control cells, transfection with PDE10 siRNA reduced cGMP hydrolysis by ~35% in both HCT116 and HT29 cell lines, but did not affect cGMP hydrolysis in colonocytes; siRNA did not significantly affect cAMP degradation in all 3 cell lines. Conclusions: PDE10 plays a role in colon tumorgenesis whereby inhibitors can selectively suppress tumor cell growth. The mechanism by which PDE10 inhibition affects growth appears to involve activation of cGMP/PKG signalling. PDE10 represents a novel anticancer target for the treament and prevention of colon cancer.

Download Full-text

Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis

Cells ◽

10.3390/cells10051213 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1213

Author(s):

Zihe Huo ◽

Mariana Sá Santos ◽

Astrid Drenckhan ◽

Stefan Holland-Cunz ◽

Jakob R. Izbicki ◽

...

Keyword(s):

Esophageal Carcinoma ◽

Tumor Cells ◽

Cell Lines ◽

Adhesion Strength ◽

Primary Tumor ◽

Carcinoma Cell ◽

Metastatic Potential ◽

Primary Tumors ◽

Metastatic Cell ◽

Carcinoma Cell Lines

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.

Download Full-text

Detection of Lymph Node Micrometastases and Isolated Tumor Cells in Sentinel and Nonsentinel Lymph Nodes of Colon Cancer Patients

World Journal of Surgery ◽

10.1007/s00268-005-0094-x ◽

2005 ◽

Vol 29 (9) ◽

pp. 1172-1175 ◽

Cited By ~ 32

Author(s):

Andreas Bembenek ◽

Ulrike Schneider ◽

Stephan Gretschel ◽

Joerg Fischer ◽

Peter M. Schlag

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Cancer Patients ◽

Tumor Cells ◽

Isolated Tumor Cells ◽

Lymph Node Micrometastases

Download Full-text

Detection of Tumor Cells in Lymph Nodes of Colon Cancer Patients Using Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction

Colorectal Cancer ◽

10.1007/978-1-4020-9545-0_16 ◽

2009 ◽

pp. 257-268

Author(s):

Lina Ohlsson ◽

Anne Israelsson ◽

Åke Öberg ◽

Marie-Louise Hammarström ◽

Gudrun Lindmark ◽

...

Keyword(s):

Colon Cancer ◽

Polymerase Chain Reaction ◽

Lymph Nodes ◽

Real Time ◽

Cancer Patients ◽

Tumor Cells ◽

Reverse Transcription ◽

Chain Reaction ◽

Polymerase Chain

Download Full-text

Cold atmospheric plasma treatment inhibits growth in colorectal cancer cells

Biological Chemistry ◽

10.1515/hsz-2018-0193 ◽

2018 ◽

Vol 400 (1) ◽

pp. 111-122 ◽

Cited By ~ 10

Author(s):

Christin Schneider ◽

Stephanie Arndt ◽

Julia L. Zimmermann ◽

Yangfang Li ◽

Sigrid Karrer ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Plasma Treatment ◽

Cancer Cells ◽

Ex Vivo ◽

Atmospheric Plasma ◽

Normal Colon ◽

Colon Tissue ◽

Cold Atmospheric Plasma ◽

Colorectal Cancer Cells

AbstractPlasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter – a device particularly developed for the treatment of tumor cells – that uses the Surface Micro Discharge (SMD) technology for plasma production in air. The present study analyzed the effects of plasma on colorectal cancer cellsin vitroand on normal colon tissueex vivo. Plasma treatment had strong effects on colon cancer cells, such as inhibition of cell proliferation, induction of cell death and modulation of p21 expression. In contrast, CAP treatment of murine colon tissueex vivofor up to 2 min did not show any toxic effect on normal colon cells compared to H2O2positive control. In summary, these results suggest that the miniFlatPlaSter plasma device is able to kill colorectal cancer cells independent of their p53 mutation status. Thus, this device presents a promising new approach in colon cancer therapy.

Download Full-text

Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer

Biomedicines ◽

10.3390/biomedicines8040086 ◽

2020 ◽

Vol 8 (4) ◽

pp. 86 ◽

Cited By ~ 1

Author(s):

Sang-Hyeon Nam ◽

Jin-Kyung Kim

Keyword(s):

Colon Cancer ◽

Experimental Colitis ◽

Therapeutic Effects ◽

Mrna Levels ◽

Colon Tissue ◽

Colon Tumorigenesis ◽

Inflammatory Status ◽

Tussilago Farfara ◽

Preventive Activity ◽

Induced Apoptosis

Background: Tussilagone, a major component of Tussilago farfara L., has anti-angiogenic and anti-inflammatory effects. However, the therapeutic and preventive activity of tussilagone in colitis-associated colon carcinogenesis is unknown. Methods: We intended to investigate the therapeutic effects and the potential mechanism of action underlying the pharmacological activity of tussilagone on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). We injected BALB/c mice with AOM and administered 2% DSS in drinking water. The mice were given tussilagone (2.5 and 5 mg/kg body weight) and colon tissues was collected at 72 days. We used Western blotting, immunohistochemistry and real-time RT-PCR analyses to examine the tumorigenesis and inflammatory status of the colon. Results: Tussilagone administration significantly reduced the formation of colonic tumors. In addition, tussilagone treatment markedly reduced the inflammatory mediators and increased heme oxygease-1 in protein and mRNA levels in colon tissues. Meanwhile, nuclear NF-κB-positive cells were elevated and nuclear Nrf2-positive cells were demised by tussilagone treatment in colon tissues. Tussilagone also reduced cell proliferation, induced apoptosis and decreased the β-catenin expression. Conclusions: Tussilagone administration decreases the inflammation and proliferation induced by AOM/DSS and induced apoptosis in colon tissue. Overall, this study indicates the potential value of tussilagone in suppressing colon tumorigenesis.

Download Full-text