Abstract P1-07-32: Activated thrombin activatable fibrinolysis inhibitor is a novel anti-metastatic factor in breast cancer
Notice bibliographique
Résumé
Abstract Thrombin activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen initially known for its role in attenuating fibrinolysis. Activated TAFI (TAFIa) is formed through proteolytic cleavage by thrombin, plasmin or, its most effective activator, thrombin in complex with the endothelial cofactor thrombomodulin (TM). TAFIa is a carboxypeptidase, which acts by cleaving carboxyl terminal lysine and arginine residues from protein and peptide substrates, including plasminogen binding sites on cell surface receptors. Carboxyl terminal lysine residues play a vital role in accelerating plasminogen activation to plasmin on the cell surface. Plasmin has many critical functions including cleaving components of the extracellular matrix (ECM), which enhances invasion and migration of cancer cells. In addition, plasmin can activate matrix metalloproteinases (MMPs), which also play a role in degrading the ECM. Furthermore, the expression of TM in tumours is inversely correlated to metastasis. Studies have shown that the anti-metastatic effects of TM result from its ability to bind thrombin. Given that the thrombin/TM complex is responsible for the activation of TAFI, the anti-metastatic effects of TM may be modulated by TAFIa. We therefore hypothesize that the activation of TAFI on the cell surface inhibits plasminogen activation and decreases breast cancer cell invasion and migration. Expression of TAFI and TM were assessed in breast cancer cells with varying degrees of metastatic potential. Although TAFI mRNA levels did not correlate with malignancy, TM mRNA levels were found to be inversely correlated with breast cancer cell malignancy. Moreover, cell invasion and migration of MDA-MB-231 and SUM149 cells were assessed upon treatment with potato tuber carboxypeptidase inhibitor (PTCI), which is a specific inhibitor of TAFIa. Inhibition of TAFIa resulted in a significant increase in cell invasion and migration of both cell lines. Cell invasion and migration of MDA-MB-231 and SUM149 cells were also assessed upon treatment with TM. Treatment with TM significantly decreased cell invasion and migration of both MDA-MB-231 and SUM149 cells. Additionally, experiments using a fluorogenic collagen substrate showed an increase in extracellular collagen cleavage after PTCI treatment, using both MDA-MB-231 and SUM149 cells. Furthermore, the ability of TAFIa to inhibit pericellular plasminogen activation was evaluated. Plasminogen activation was significantly decreased on the surface of MDA-MB-231 and SUM149 cells following treatment with various concentrations of TAFIa. Taken together, these results indicate a vital role for TAFIa in regulating pericellular plasminogen activation and ultimately ECM proteolysis. Enhancement of TAFI activation in the breast cancer tumour microenvironment may be a therapeutic strategy to inhibit invasion and prevent metastasis of breast cancer cells. Citation Format: Zainab A Bazzi, Deborah Rudy, Lisa A Porter, Dora Cavallo-Medved, Michael B Boffa. Activated thrombin activatable fibrinolysis inhibitor is a novel anti-metastatic factor in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-32.
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 | 0,001 |
| 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 ».