Abstract 3832: A tissue injury-like state in mouse with BMP signaling impaired Foxl1+ telocytes leads to abnormal ECM biodynamics and neoplasia initiation
Notice bibliographique
Résumé
Abstract "Tumors are wounds that do not heal" is an accepted concept where the tumor stroma composition bears a resemblance to the granulation tissue of healing wounds. Most of the solid cancers can be associated with a reorganization of the extracellular matrix (ECM) within the tumor leading to fibrosis and increased tissue stiffness, contributing to disease malignancy. Colorectal cancer (CRC) makes no exception to this microenvironment reorganization. The colon stroma is home to multiple cell types involved in ECM biodynamics such as the FoxL1+ Telocytes (TCFoxL1+) which form a network underneath the epithelium, contributing to the microenvironment that supports epithelial and immune cell homeostasis. Our group already showed, in a mouse model of CRC, that BMPR1A signaling deletion in TCFoxL1+ influences the microenvironment via stromagenesis, immune infiltration and colonic dysplasia. However, the precise biomolecular and biomechanical events that contributes to the onset of this state have yet to be identified. We aimed to identify the early-onset dysplastic modulations in ECM biodynamics induced by BmpR1a-deficient TCFoxL1+ (BmpR1aΔFoxL1+) in mouse colonic mucosa. Matrisomics analysis was thus performed to determine the inventory of ECM proteins expressed solely in the GI stroma following tissue deconstruction of control and BmpR1aΔFoxL1+ mice colons. Characterization of the collagen network and matrisome-associated modulations was evaluated by histological and biochemical methods. Presence of bacteria invading the mucosa was studied by Fluorescence In Situ Hybridization (FISH). Matrisome proteins that were differentially regulated indicate an enrichment for proteins involved in collagen network regulation, wound repair homeostasis and immune response. Increased deposition of collagen, presence of thicker fibers realigned into linear patterns were observed in BmpR1aΔFoxL1+ mouse colon, leading to change in tissue stiffness and biomechanics. Abnormal presence of unfolded collagen with a concomitant increase in a collagen-folding chaperone was also observed. Validations of proteins involved in fibrin clot formation as well as immune response mediators such as S100A9 indicate that BmpR1aΔFoxL1+ mice deal with tissue micro-injuries and inflammation that is unresolved, creating an unfavorable microenvironment for tissue homeostasis leading to neoplasia initiation. Taken together, these results suggest that Bmp-signaling deficient TCFoxL1+ significantly contribute to the collagen network biodynamics through increased collagen deposition, fiber alignment reorganization and regulation of the triple-helix assembly. Other matrisome modulations suggest a state of unresolved wound healing due to tissue injury, that could be the etiology of GI pathology such as CRC and lead to more severe conditions upon various environmental triggers. Citation Format: Veronique Pomerleau, Vilcy Reyes Nicolas, Carla-Marie Jurkovic, François-Michel Boisvert, Nathalie Perreault. A tissue injury-like state in mouse with BMP signaling impaired Foxl1+ telocytes leads to abnormal ECM biodynamics and neoplasia initiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3832.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,002 |
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 ».