Abstract LB-252: Expression of FGF-2 is essential for the maintenance of cancer stem cell characteristics in human colorectal tumor cell lines
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".