Abstract LB-252: Expression of FGF-2 is essential for the maintenance of cancer stem cell characteristics in human colorectal tumor cell lines
Notice bibliographique
Résumé
Abstract Colorectal cancers (CRCs) consist of tumor cells with different capabilities. A small subpopulation of these tumor cells is characterized by signs of dedifferentiation and is able to induce in small numbers heterogeneous tumors when implanted subcutaneously into immunocompromised mice. This subpopulation of tumor cells is known to resemble cancer stem cells (CSCs). CSCs from colorectal cancers (CoCSCs) are considered to be characterized by nuclear ß-CATENIN, the central effector protein of the WNT signaling pathway that is dysregulated in most colorectal carcinomas. Interestingly, nuclear ß-CATENIN induces epithelial-mesenchymal transition (EMT) which is known to be intimately associated with the induction of stemness in formerly epithelial cells. Therefore, a mechanism mediated by stabilized ß-CATENIN might render CoCSCs independent of adequate WNT regulated niche conditions as they are known to be important for their normal counterparts in the intestine. Importantly, for in vitro maintenance of CoCSCs the addition of FGF-2 (fibroblast growth factor-2) to the culture medium is mandatory for their dedifferentiated phenotype. Since we detected that FGF-2 is a ß-CATENIN target gene and thus endogenously expressed by colorectal tumor cells, we hypothesized that this endogenous FGF-2 might be part of the ß-CATENIN regulated mechanism for the maintenance of CSC characteristics also in cultivated colorectal tumor cell lines. In a first experimental approach, we prepared side populations (sp) from Caco2 and LoVo cells. Sp are known to contain CSCs. Our sp cells did not only express higher levels of the CoCSC markers CD44, CD166 and CD133 but also significantly increased values of FGF-2. To investigate the importance of FGF-2 we stably knocked down (kd) the FGF-2 expression in LoVo and Caco2 cells using RNA interference (RNAi). Knock down of FGF-2 led to a strong reduction in anchorage independent growth as well as tumor formation after xenografting into nude mice indicative for a less transformed phenotype. Moreover, LoVo FGF-2 kd cells displayed less mesenchymal characteristics like downregulation of vimentin and upregulation of E-cadherin at the same time as shown by real time PCR, Western Blotting and immunofluorescence. Importantly, the sp and thus the CSC fraction from LoVo FGF-2 kd cells was almost 90% reduced compared to the control cell line. Taken together, we show evidence that the ß-CATENIN target gene FGF-2 is implicated in the transformation of colorectal tumor cells and is also important for the maintenance of mesenchymal- as well as CSC characteristics. Our results are thus another piece of evidence for the outstanding role of ß-CATENIN in colorectal carcinogenesis and might offer potential therapeutic strategies against one of its important downstream effectors that obviously plays an important role in the generation of an autonomous, ß-CATENIN regulated CSC niche. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-252.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».