Abstract 1950: Differential expression of MUC16 mucin (CA125) depending on the architecture of the tumors developed in an orthotopic mouse model of high-grade serous ovarian cancer
Notice bibliographique
Résumé
The histopathology of high-grade serous ovarian cancer (HGSOC) in orthotopic mouse models has received limited attention. Using immunosuppressed mice, we generated intraperitoneal HGSOC disease that includes formation of ascites and/or pleural effusions, together with a myriad of intra-abdominal growths. We studied 3 HGSOC cell lines evolved from the same patient along disease progression—a platinum-sensitive, PEO1; a platinum-resistant after further relapse, PEO4; and another at the end of life, PEO6. We found that the animals were prone to develop the disease sooner when implanted with cells obtained from the most advanced disease. Using these models, we characterized the histopathology of the masses preferably developed in the stomach-spleen-pancreas region enclosing the omentum. Other sites of tumor formation we found where the lower pelvic cavity, the peritoneal wall, the liver base, the diaphragm, the lungs, the uterus, and the ovaries. The architecture of the tumors was more often represented by slit-like fenestrations, yet certain zones displayed papillary, glandular, or solid structures sometimes including infiltrating lymphocytes. When we studied the expression of antigen CA125, we found that its pattern of staining was highly heterogeneous. In PEO1/4/6 cells maintained in culture CA125 was expressed in all cell types, yet with a major abundance aligned with disease evolution. In vivo, within the tumors, the expression of CA125 was mostly limited to the apical region of cells facing slit-like spaces generated in between solid sheets of tumor cells surrounded by fibrovascular stroma. When tumor cells were located deep within homogeneous solid masses devoid of slit-like fenestrations, they usually did not express CA125. In contrast, when cells were found gathered as multicellular structures free-floating in open spaces surrounding target organs—e.g. within the bursa around the ovaries—CA125 was highly expressed. This is coincident with the high expression of CA125 observed in vitro in cells spontaneously forming multicellular aggregates in suspension. It is likely that HGSOC cells express CA125 to face or invade into open spaces. In summary, this work reveals tissue heterogeneity and polarity in the expression of CA125 in solid tumors of HGSOC developed in immunosuppressed mice. This selected pattern of expression may be related to the oncogenic functions of CA125 (a.k.a. MUC16, a glycoprotein), such as protecting cells from immunological attacks, or promoting metastases by binding to mesothelin produced by mesothelial cells that line the peritoneal cavity.Citation Format: Alicia A. Goyeneche, Michael A. Lisio, Zu-hua Gao, Carlos M. Telleria. Differential expression of MUC16 mucin (CA125) depending on the architecture of the tumors developed in an orthotopic mouse model of high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1950.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 0,000 |
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 tête enseignante, 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 ».