Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression

Abstract

Previous observations made in human and mouse colons suggest that reelin protects the colon from pathology. In this study, we evaluated reelin expression during the transition from either colitis or precancerous lesions to colon cancer and tried to elucidate reelin regulation under these transition processes. Samples of healthy and pathological colons from humans and mice treated with either azoxymethane/dextran sulfate sodium (DSS) or azoxymethane alone were used. The relative abundances of reelin, DNMT-1 and ApoER2 mRNAs were determined by PCR in the colon samples cited above and in the tissue adjacent to mouse colon polyps and adenocarcinomas. In both, humans and mice, reelin mRNA abundance increased significantly in ulcerative colitis and slightly in polyps and decreased in adenomas and adenocarcinomas. Reelin expression was higher in the tissue adjacent to the colon adenocarcinoma and lower in the lesion itself. The reelin expression changes may result, at least in part, from those in DNMT-1 and appear to be independent of ApoER2. Lack of reelin downregulated p-Akt and p53 in healthy colon and prevented their increases in the inflamed colon, whereas it increased GSK-3β in DSS-untreated mice. In conclusion, reelin mRNA abundance depends on the severity of the colon pathology, and its upregulation in response to initial injuries might prevent the beginning of colon cancer, whereas reelin repression favors it. Increased p53 expression and activation may be involved in this protection. We also propose that changes in colon reelin abundance could be used to predict colon pathology progression.

New proteins in the differentiation of papillary renal cell carcinoma from clear cell renal cell carcinomas; Importance of DARS2, Reelin and Enkurin

“…In a recent study, it was stated that an increase in reelin prevents the development of colon cancer, and its decrease might trigger the formation of colon carcinoma, and it was suggested as a biomarker in the prediction of prognosis. [14] In the present study, it was found that reelin was more expressed in papillary RCC, but the expression decreased in clear cell carcinoma, which is a more aggressive tumor, compared to papillary RCC, and the difference between them was statistically significant. Decreased expression of reelin in clear cell RCC, which is quite aggressive, is a finding that was expected, and it was in line with the literature data.…”

Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases

“…These are common risk factors for cardiovascular disease [130][131][132][133][134][135], pulmonary hypertension [136][137][138][139][140][141][142][143], and stroke [130], of which Reelin lowering could predictably affect in a favorable manner. However, the literature reveals a multifaceted role for Reelin in cancer development [41], with studies suggesting both promotional [144][145][146][147][148][149][150][151][152][153] and inhibitory [62,[154][155][156][157][158][159] effects on malignant cell behavior depending on the cell type and affected organ. Therefore, dedicated studies should assess whether cancer might represent a medical contraindication for future anti-Reelin therapies.…”

“…Reelin is also abundant in the blood with a typical concentration of around 10 ng/mL in humans [53], and exercises function outside of the CNS [51,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71]. In the past 10 years, three major non-neuronal functions for plasma Reelin have been described in inflammation, vascular tone regulation, and thrombosis.…”