The thrombin cleavage domain of osteopontin is important for mediating growth and adhesive properties of human breast cancer cells
Notice bibliographique
Résumé
3432 Osteopontin (OPN) is a secreted phosphoprotein that has been associated with malignancy of breast and other cancers. OPN contains several conserved structural domains, including two integrin-binding sites and a thrombin cleavage site located in close proximity to each other. Recent evidence indicates that thrombin, commonly known for its proteolytic role in coagulation, may also play an important role in tumor growth and metastasis. The presence of a thrombin cleavage site in the OPN backbone suggests that the function of OPN may rely, at least in part, on its interaction with thrombin. The purpose of this study was to determine if OPN-mediated malignancy depends on conservation of the thrombin cleavage site within OPN. MDA-MB-468 human breast cancer cells were stably transfected to overexpress wildtype OPN (468-OPN), mutant OPN containing a deleted thrombin cleavage site (468-ΔTC), or a control vector (468-CON). Pooled populations of 468-OPN, 468-ΔTC, and 468-CON cells were compared for functional differences in malignant behavior in vitro, including cell proliferation, plating efficiency (colony formation), and cell adhesion. Proliferation assays demonstrated that there was no significant difference in doubling time between the three cell lines. However, an extended lag phase in the growth of 468-ΔTC cells was observed relative to 468-OPN and 468-CON cells. In plating efficiency assays, overexpression of either wildtype OPN or thrombin-uncleavable OPN resulted in the formation of a significantly greater number of colonies relative to control, but the mean diameter of the colonies formed by 468-ΔTC cells was significantly less than colonies formed by 468-OPN cells. Overexpression of wildtype OPN also resulted in significantly increased cell adhesion to vitronectin, and this adhesion was dependant on conservation of the thrombin cleavage site. Differences in cell growth and adhesion were specific to the interaction between OPN and thrombin, since treatment with the thrombin-specific inhibitor Argatroban caused 468-OPN cells to develop an extended lag phase of growth similar to that shown by 468-ΔTC cells, as well as significantly reducing their adhesion to vitronectin. In contrast, treatment with Argatroban had little effect on the growth or adhesion of 468-ΔTC and 468-CON cells. These novel findings indicate that the thrombin cleavage site in OPN is important for mediating growth and adhesive properties of MDA-MB-468 breast cancer cells in vitro, potentially by increasing accessibility to adjacent integrin-binding sites. Ongoing studies are aimed at determining the involvement of integrins, as well as investigating the role of thrombin in OPN-mediated malignancy in vivo. These studies complement clinical findings in our laboratory that have identified OPN as an important prognostic indicator and potential therapeutic target in breast cancer patients.
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 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 ».