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.

Man har undersøkt hvilken rolle fibroblastvekstfaktor 2 (FGF2) spiller i selvfornyelsen av stamceller fra kolorektal kreft.

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.

Gener som er direkte assosiert med EMT sammen med en mesenkymal og selvfornyende fenotype (TGFB3, ID1, ID2 og ID4) ble funnet å være overuttrykt i organoider.

Mens FGFR-hemming førte til økt MAPK-signalering, observerte de indusert differensiering, tap av de fleste stamcellemarkører og en epitelial fenotype.

Kreftstamceller er en subpopulasjon av ondartede celler som er i stand til å fornye seg selv og fungere som en kontinuerlig kilde for differensierte tumorceller. I noen protokoller for CSC-dyrking er fibroblastvekstfaktor 2 en viktig ingrediens for å opprettholde stamcellene.

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 konsekutive, uselekterte CRC-pasienter deltok i undersøkelsen.

Kontroller originalartikkel her.

Grafisk sammendrag drevet av Mind the Graph

Laget med Mind the Graph

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 a 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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