The Disabled spheroid and organoid formation by FGFR-inhibition in patient-derived CRC cells is much easier to understand using Mind the Graph’s illustrations.
The scheme created by the author shows that the surgical biopsies were enzymatically digested to obtain a suspension of single cells. The naïve unsorted cells were cultured in FGF2 containing CSC-medium or with the FGFR-inhibitor SU-5402.
The role of fibroblast growth factor 2 (FGF2) in the self-renewal of colorectal cancer stem cells has been investigated
In ‘FGF Signalling in the Self-Renewal of Colon Cancer Organoids’, Jörg Otte and colleagues (2019) reported that when naïve single cells were embedded in Matrigel and cultured in the CSC-medium, a more complex self-organization was observed in all patients analysed.
Genes directly associated with EMT together with a mesenchymal and self-renewing phenotype (TGFB3, ID1, ID2 and ID4) were found to be overexpressed in organoids.
While FGFR-inhibition led to an enhanced MAPK signalling, they observed induced differentiation, a loss of most stem cell markers and an epithelial phenotype.
Cancer stem cells are a subpopulation of malignant cells able to self-renew and to serve as an ongoing source for differentiated tumour cells. In some protocols of CSC culture, Fibroblast growth factor 2 is an important ingredient for maintaining stemness.
In CSC-medium cultured organoids, on the other hand, they detected induction of TGF-β and of all four members of the inhibitor-of-differentiation gene family.
9 consecutive unselected CRC patients were involved in the research.
Check the original article here.
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Some of their conclusions potentially strengthen what was previously known about this field: “The pluripotency-associated genes NANOG, LIN28 and SALL1 were exclusively expressed by hESCs. The GO-terms “negative regulation of BMP signaling pathway” and “SMAD protein signal transduction” were detected in our hESC culture,” Otte suggested.
The authors admit that “GO-term analysis of this gene-set yielded only few significant results due to the low number of commonly regulated genes. Most of these GO-terms for the CSC-medium condition were associated with active transcription, cell proliferation or increased glucose uptake.
After FGFR-inhibition, we found cell-cycle regulators as well as many genes annotated with “epithelial cell differentiation”, “digestion” or “bile acid and bile salt transport”.”
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