scholarly journals Specific tumor-derived CCL2 mediated by pyruvate kinase M2 in colorectal cancer cells contributes to macrophage recruitment in tumor microenvironment

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769596 ◽  
Author(s):  
Kejian Zou ◽  
Yaodong Wang ◽  
Yan Hu ◽  
Liansheng Zheng ◽  
Wanfu Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Pyruvate Kinase ◽  
Quantitative Polymerase Chain Reaction ◽  
Nuclear Factor Κb ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cancer Tissue ◽  
Nuclear Factor ◽  
Pyruvate Kinase M2 ◽  
Macrophage Recruitment

Development of colorectal cancer has been considered as a result of imbalance of pro- and anti-inflammatory intestinal microenvironment accompanied by macrophage recruitment. Despite macrophages are implicated in remodeling tumor microenvironment, the mechanism of macrophage recruitment is not fully elucidated yet. In this study, we reported clinical association of highly expressed pyruvate kinase M2 in colorectal cancer with macrophage attraction. The conditioned medium from Caco-2 and HT-29 cells with depleted pyruvate kinase M2 dramatically reduced macrophage recruitment, which is reversed by addition of, a critical chemotaxis factor to macrophage migration, rCCL2. Silencing of endogenous pyruvate kinase M2 markedly decreased CCL2 expression and secretion by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Endogenous pyruvate kinase M2 interacted with p65 and mediated nuclear factor-κB signaling pathway and mainly regulated phosphorylation of Ser276 on p65 nuclear factor-κB. In addition, inhibition of macrophage recruitment caused by pyruvate kinase M2 silencing was rescued by ectopic expression of p65. Interestingly, pyruvate kinase M2 highly expressed in colorectal cancer tissue, which is correction with macrophage distribution. Taken together, we revealed a novel mechanism of pyruvate kinase M2 in promoting colorectal cancer progression by recruitment of macrophages through p65 nuclear factor-κB–mediated expression of CCL2.

scholarly journals Expression of tumor pyruvate kinase M2 isoform in plasma and stool of patients with colorectal cancer or adenomatous polyps

2019 ◽  
Author(s):  
Farideh Rigi ◽  
Aliakbar Jannatabad ◽  
Azra Izanloo ◽  
Reza Roshanravan ◽  
Hamid Reza Hashemian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pyruvate Kinase ◽  
Sensitivity And Specificity ◽  
Adenomatous Polyps ◽  
Plasma Samples ◽  
Proliferating Cells ◽  
Pyruvate Kinase M2 ◽  
Specificity And Sensitivity ◽  
Tumor Group ◽  
Stool Samples

Abstract Background: Tumor pyruvate kinase M2 isoform (tM2-PK), which is an isoform of PK-glycolytic enzyme and appears on the surface of cancerous proliferating cells, has been used as a diagnostic biomarker for colorectal cancer (CRC). The aim of this study was to evaluate the tM2-PK measurement test for the diagnosis of CRCs and adenomatous polyps in plasma and stool samples in an Iranian population. Methods: In this prospective study, a total of 226 stool and 178 plasma samples were received from patients referred to colonoscopy units. tM2-PK enzyme was measured using two separate ScheBo-Biotech-AG ELISA kits for stool and plasma samples. Results: At the cut-off value of 4 U/ml, in tumor group, the sensitivity of fecal tM2-PK test was 100% and the specificity was 68%, and in polyp group, the sensitivity and specificity were 87% and 68%, respectively. At the cut-off value of 15 U/ml in tumor group, the sensitivity of plasma tM2-PK test was 98% and specificity was 74% and in polyp group the sensitivity and specificity were 98% and 74%, respectively. Based on our results, a cut-off range of 4.8-8 U/ml and >8 U/ml could be used to detect polyp and tumor in stool samples, respectively. Similarly, a cut-off range of 19-25 U/ml and >25 U/ml is recommended in plasma samples for polyp and tumor detection, respectively. Conclusions: This study revealed a high specificity and sensitivity of tM2-PK test for stool and plasma samples in patients with CRC and polyps suggesting it as a non-invasive assay to diagnose CRC and adenomatous polyps.

scholarly journals Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment

2019 ◽  
Vol 12 (2-3) ◽  
pp. 149-167 ◽  
Author(s):  
Mohd Rihan ◽  
Lakshmi Vineela Nalla ◽  
Anil Dharavath ◽  
Amit Shard ◽  
Kiran Kalia ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Pyruvate Kinase ◽  
Pyruvate Kinase M2

Computational analysis of nuclear factor-κB and resveratrol in colorectal cancer

2020 ◽  
pp. 1-9
Author(s):  
Begum Dariya ◽  
Santosh Kumar Behera ◽  
Gowru Srivani ◽  
Batoul Farran ◽  
Afroz Alam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computational Analysis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor

scholarly journals Effects of Linalyl Acetate on Thymic Stromal Lymphopoietin Production in Mast Cells

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1711 ◽  
Author(s):  
Phil-Dong Moon ◽  
Na-Ra Han ◽  
Jin Lee ◽  
Hyung-Min Kim ◽  
Hyun-Ja Jeong
Keyword(s):  
Intracellular Calcium ◽  
Inflammatory Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Allergic Diseases ◽  
Nuclear Factor Κb ◽  
Thymic Stromal Lymphopoietin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Linalyl Acetate ◽  
Caspase 1 ◽  
Wide Range

Thymic stromal lymphopoietin (TSLP) is an important factor responsible for the pathogenesis of allergic diseases, such as atopic dermatitis and asthma. Because linalyl acetate (LA) possesses a wide range of pharmacological properties, being antispasmodic, anti-inflammatory, and anti-hyperpigmentation, we hypothesized that LA could inhibit TSLP. Therefore, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, Western blot analysis, fluorescent analyses of the intracellular calcium levels, and the phorbol myristate acetate (PMA)-induced edema model were used to investigate how LA inhibits the production of TSLP in HMC-1 cells. LA reduced the production and mRNA expression of TSLP in HMC-1 cells. LA also inhibited the activation of nuclear factor-κB and degradation of IκBα. PMA plus A23187 stimulation up-regulated caspase-1 activity in HMC-1 cells; however, this up-regulated caspase-1 activity was down-regulated by LA. Finally, LA decreased intracellular calcium levels in HMC-1 cells as well as PMA-induced ear swelling responses in mice. Taken together, these results suggest that LA would be beneficial to treatment of atopic and inflammatory diseases by reducing TSLP.

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