Abstract 50: Tumorigenic properties of uveal melanoma cancer cells cultured in 3D or on a reconstructed extracellular matrix
Bibliographic record
Abstract
Abstract Background: Uveal melanoma (UM) is the most common intraocular tumor in adults. It arises from the transformation of melanocytes, and despite the effective treatment of the ocular tumor, hepatic metastases lead to a poor prognosis. Our hypothesis is that the invasive potential and therapeutic resistance of UM cells (UMCs) depend on interactions with stromal cells and properties of the extracellular matrix (ECM). Our study aims to determine the impact of UMCs in stromal cell activation, and to define the role of the ECM produced by choroidal fibroblasts or hepatic stellate cells (HSteCs) on UM cell proliferation and invasion. Methods: Two types of tumor spheroids were generated i) one corresponding to primary melanoma (UMCs from eye tumor + choroidal fibroblasts and endothelial cells) and ii) the other to liver metastasis (UMCs from liver metastasis + HSteCs and sinusoidal endothelial cells). The organization of these mixed spheroids were studied by confocal microscopy using the following markers: Melan-A (UM cells), alpha-smooth muscle actin (aSMA; activated fibroblasts and stellate cells), CD31 (endothelial cells) and Ki67 (proliferation). The viability and invasion capacity of the mixed spheroids were analyzed using an ATP consumption assay, and the measurement of the invasion area in Matrigel. Next, two types of matrices were produced by tissue engineering using the self-assembly approach with choroidal fibroblasts or HSteCs. These matrices were devitalized and characterized by confocal microscopy (collagens, fibronectin), before seeding UMCs to study their morphology, proliferation and ECM remodeling. Results: A higher concentration of alpha-SMA and proliferative cells were observed in the outer layers of the spheroids by immunofluorescence analyses. Choroidal and hepatic matrices were produced in 21 days. These tissue-engineered matrices contained fibronectin and collagen I. These devitalized matrices were seeded with UMCs in monolayer to study their change of morphology, proliferative state and ECM remodeling. Conclusions: We characterized the viability and cellular organization in both choroidal and hepatic spheroid models, and successfully generated tissue-engineered choroidal and hepatic matrices. With the optimization of these 3D models, we will better understand the steps involved in the progression of ocular melanoma to a metastatic stage. These complex models may replace the 2D model using tumor cells in monolayer for future drug screening, which will consider the impact of the microenvironment on UM therapeutic resistance. Citation Format: Olivier Chancy, Léo Piquet, Kelly Coutant, Andrew Mitchell, Solange Landreville. Tumorigenic properties of uveal melanoma cancer cells cultured in 3D or on a reconstructed extracellular matrix [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 50.
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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) | 0.002 | 0.000 |
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".