Abstract LB-41: Regulation of adhesion, motility, and invasion by insulin-like growth factor-2 binding protein 3 in pancreatic cancer cells
Bibliographic record
Abstract
Abstract Background: Overexpression of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3 or IMP3), a member of the VICKZ family of RNA-binding proteins, has been correlated with poor prognosis in pancreatic cancer and other cancer types, including lung, bladder, kidney, liver, and prostate. In human leukemia cells as well as in HeLa and hepatocellular carcinoma cells, IMP3 has previously been shown to regulate a number of cellular functions. However, the role of this oncofetal protein in pancreatic cancer progression remains to be elucidated. In the present study, we characterized the effect of IMP3 inhibition on the proliferation, motility, adhesion, and invasive potential of pancreatic cancer cells. Methods: IMP3 levels in Panc-1 and Hs766T were decreased through RNA interference. Untreated and scramble-siRNA transfected cells were used as controls. The effect of knockdown on cellular behavior was evaluated 48 h after transfection. Proliferation was assessed using the MTS assay, while a commercially-available colorimetric assay was used to assess adhesion to extracellular matrix proteins. Motility and invasive potential were evaluated using the Boyden chamber assay. Data were analyzed using repeated measures ANOVA. Significant F ratios were further examined using the Tukey post-hoc test. Results: The basal levels of IMP3 were found to be similar in Panc1 and Hs766T cells. IMP3 siRNA knockdown reduced IMP3 protein levels by 48% relative to scramble siRNA control. In both cell lines, a decrease in IMP3 did not significantly affect proliferation when compared to scramble siRNA-treated control. Interestingly, knockdown of IMP3 reduced the adhesion of Hs766T to fibronectin (20%; P < 0.05), tenascin (23%; P < 0.05), collagen IV (30%; P < 0.01), laminin (18%; P < 0.01), and vitronectin (51%, P < 0.01) relative to scramble siRNA control. Adhesion of Hs766T to collagen I and collagen IV) was unaffected. Moreover, relative to scramble siRNA control, the suppression of IMP3 expression in Hs766T reduced motility by 30% (P < 0.05) and cellular invasion through Matrigel by 80% (P < 0.05). In contrast, knockdown of IMP3 did not alter the adhesion, motility, and invasive potential of Panc1 cells compared to scramble siRNA control. Conclusion: Our preliminary results demonstrated that IMP3 differentially regulates cellular adhesion and invasive potential of pancreatic cancer cell lines, suggesting that this oncofetal protein may play a role in tumor metastasis. In line with this hypothesis, we are currently examining the role of IMP3 in regulating the phenotype of L3.6pl, a pancreatic cancer cell line characterized to exhibit metastatic potential. In addition, studies are currently underway to identify the downstream molecular target(s) of IMP3 that may mediate metastasis of pancreatic cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-41. doi:10.1158/1538-7445.AM2011-LB-41
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".