Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer
AbstractMicroRNA-21 (miR-21) is upregulated in many cancers including colon cancers and is a prognostic indicator of recurrence and poor prognosis. In colon cancers, miR-21 is highly expressed in stromal fibroblastic cells and more weakly in a subset of cancer cells, particularly budding cancer cells. Exploration of the expression of inflammatory markers in colon cancers revealed tumor necrosis factor alpha (TNF-α) mRNA expression at the invasive front of colon cancers. Surprisingly, a majority of the TNF-α mRNA expressing cells were found to be cancer cells and not inflammatory cells. Because miR-21 is positively involved in cell survival and TNF-α promotes necrosis, we found it interesting to analyze the presence of miR-21 in areas of TNF-α mRNA expression at the invasive front of colon cancers. For this purpose, we developed an automated procedure for the co-staining of miR-21, TNF-α mRNA and the cancer cell marker cytokeratin based on analysis of frozen colon cancer tissue samples (n = 4) with evident cancer cell budding. In all four cases, TNF-α mRNA was seen in a small subset of cancer cells at the invasive front. Evaluation of miR-21 and TNF-α mRNA expression was performed on digital slides obtained by confocal slide scanning microscopy. Both co-expression and lack of co-expression with miR-21 in the budding cancer cells was noted, suggesting non-correlated expression. miR-21 was more often seen in cancer cells than TNF-α mRNA. In conclusion, we report that miR-21 is not linked to expression of the pro-inflammatory cytokine TNF-α mRNA, but that miR-21 and TNF-α both take part in the cancer expansion at the invasive front of colon cancers. We hypothesize that miR-21 may protect both fibroblasts and cancer cells from cell death directed by TNF-α paracrine and autocrine activity. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 7386 KB)
Share & Cite This Article
Møller, T.; James, J.P.; Holmstrøm, K.; Sørensen, F.B.; Lindebjerg, J.; Nielsen, B.S. Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer. Int. J. Mol. Sci. 2019, 20, 1907.
Møller T, James JP, Holmstrøm K, Sørensen FB, Lindebjerg J, Nielsen BS. Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer. International Journal of Molecular Sciences. 2019; 20(8):1907.Chicago/Turabian Style
Møller, Trine; James, Jaslin P.; Holmstrøm, Kim; Sørensen, Flemming B.; Lindebjerg, Jan; Nielsen, Boye S. 2019. "Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer." Int. J. Mol. Sci. 20, no. 8: 1907.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.