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- Dimberg, Jan, et al.
(författare)
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Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas
- 2011
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 2:3, s. 413-418
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Tidskriftsartikel (refereegranskat)abstract
- Proteases facilitate a number of steps in cancer progression. The serine protease inhibitors (serpins) are a protein superfamily with inhibitory activity against proteases. One of these proteases, serpinA3, appears to have a multifaceted role and is associated with inflammatory reactions, Alzheimer's disease, malignant melanoma and gastric cancer. To gain insight into the potential effect of serpinA3 on colorectal cancer (CRC) we determined whether serpinA3 is altered in colorectal tissue or plasma in CRC patients. Collectively, by using ELISA we noted a significantly lower serpinA3 level in cancer tissue compared to paired normal tissue. Moreover, the tumour serpinA3 level tended to be higher in disseminated disease as compared to localised disease. No significant difference in the plasma levels of serpinA3 was noted in the patients when compared to the controls. However, plasma serpinA3 and C-reactive protein (marker of inflammation) in the CRC patients and controls were significantly positively correlated. To confirm and detect localization of serpinA3 expression, immunohistochemistry was performed. Immunohistochemistry showed heterogeneous immunoreactivity in epithelial cells in the cancer and normal tissue and extracellular staining within bands of stroma as well as in some stromal cells. A Taq Man system was used to investigate a single nucleotide polymorphism (rs4934) in the serpinA3 signal sequence gene with supposed effect on serpinA3 secretion and expression. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions, nor were associations noted between clinical characteristics and serpinA3 levels. In conclusion, an altered serpinA3 concentration in CRC tissue may be a potential biomarker in CRC progression. SerpinA3 concentrations in plasma appear to be correlated with systemic inflammation, but do not appear to be specific to CRC patients. Further studies are warranted to improve our understanding of the role of serpinA3 in CRC.
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- Dimberg, Jan, et al.
(författare)
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Polymorphisms of Fractalkine receptor CX3CR1 and plasma levels of its ligand CX3CL1 in colorectal cancer patients
- 2007
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 22:10, s. 1195-1200
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS:The chemokine Fractalkine/CX3CL1, which is expressed by epithelial cells within normal colorectal mucosa and in colorectal cancer (CRC), is thought to have a crucial role in colorectal mucosal immunity by recruiting leucocytes via the receptor CX3CR1. The purpose of this study was to investigate two single-nucleotide polymorphisms of the Fractalkine receptor/CX3CR1 gene, V249I and T280M, in CRC to find out whether they occur more often in patients with CRC than in non-CRC individuals. In the search for tumour markers, we also intended to determine whether plasma levels of Fractalkine were correlated with parameters such as Dukes' stage, tumour localisation, gender and age in CRC patients.MATERIALS AND METHODS:Genomic deoxyribonucleic acid from 223 CRC patients and 229 controls was amplified by polymerase chain reaction, and the polymorphisms were detected by the restriction fragment length polymorphism analysis. Fractalkine/CX3CL1 was analysed in plasma from 62 CRC patients and 78 controls using enzyme-linked immunosorbent assay.RESULTS:The variant V249I was significantly different in genotype and allelic distribution between CRC patients and control subjects, P = 0.028 and P = 0.048, respectively. We also found that individuals with the I249 allele in homozygote state were less frequent in the CRC group (3.1%) compared with controls (9.2%; P = 0.008). No significant difference was observed regarding Fractalkine/CX3CL1 levels in plasma between patients and the control group.CONCLUSION:Our results suggest that the lack of the allele I249 of the CX3CR1 gene may play a partial or minor role in CRC and that plasma Fractalkine/CX3CL1 does not seem to be a useful tumour marker that reflects the disease outcome of CRC.
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- Mumtaz, Melad, et al.
(författare)
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Decreased expression of the chemokine CCL21 in human colorectal adenocarcinomas
- 2009
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 21:1, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have revealed participation of chemokines in cancer by regulating leukocyte movement to modify local immunoresponse. The chemokine CCL21 has been identified to play a pivotal role in homing and localization of immune cells to lymphoid tissue and into organ of non-lymphoid origin. In the cancer biology CCL21 seems to have multifaceted roles. CCL21 attracts CCR7 bearing cells especially T and dendritic cells but also various cancer cells. Besides the antitumour role as leukocyte recruiting, CCL21 has been shown to facilitate dendritic cell functions and to exert an angiostatic effect. To gain insight into the possible influence of CCL21 oil colorectal cancer (CRC) we determined whether the CCL21 is altered in CRC tissue. Collectively, by using ELISA we noted a significant lower CCL21 level in cancer tissue compared with paired normal tissue. Patients with a tumour localized in the rectum revealed significantly lower level of CCL21 than patients with a tumour localized in the colon both compared with paired normal tissue. We used immunohistochemistry and found heterogeneous immunoreactivity predominantly within areas of stromal cells mainly in macrophages. We also used a TaqMan system to investigate two single-nucleotide polymorphisms rs 11574915 and rs 2812377 with Supposed effect on CRC. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions or associations to clinical characteristics or CCL21 tissue levels. Our study implied that lower level of CCL21 in CRC tissue supports the idea that cancer is related to immunodeficiency probably depending on regulatory factors produced by tumour cells and that the different levels of CCL21 in rectum and colon may reflect divergent mechanisms in colorectal carcinogenesis. Further studies are needed to clarify whether the CCL21 level has an impact on CRC progression and survival rate.
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