Abstract B10: Soluble lung-derived factors mediate breast cancer cell migration and growth via CD44 receptor-ligand interactions
Notice bibliographique
Résumé
Abstract Background: The majority of breast cancer deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, where preferential secondary sites include the lymph node, lung, liver, bone, and brain. However, it is not clear whether properties of the cancer cells (the “seeds”); properties of the organ microenvironment (the “soil”), or a combination of both are responsible for this observed organ tropism of breast cancer. It has been proposed that small subsets of stem-like tumor cells are responsible for tumor initiation and progression. In breast cancer, these cells are identified by their high aldehyde dehydrogenase (ALDH) activity and/or CD44+CD24- phenotype. We have previously shown that ALDHhiCD44+ breast cancer cells exhibit key metastatic behaviors in vitro and in vivo. However, the mechanisms underlying the organ-specific metastatic capacity of these cells requires further elucidation. Hypothesis: Breast cancer cells exhibit differential growth and migration patterns in specific organ microenvironments; and ALDHhiCD44+ breast cancer cells exhibit increased organ-specific migration and growth (1) preferentially in the lung microenvironment and (2) compared to their ALDHlowCD44- counterparts. Methods: A novel ex vivo model system comprised of organ-conditioned media generated from athymic nude mice was used to test organotropic migration/growth of whole populations of MDA-MB-231, MDA-MB-468, SUM149, and SUM159 human breast cancer cell lines, and ALDHhiCD44+ and ALDHlowCD44- populations isolated from the MDA-MB-231 cell line. Protein arrays were used to interrogate lung-conditioned media and identify soluble factors of interest. Bead-based immunodepletion of target proteins was performed on lung-conditioned media. The migration/growth response of MDA-MB-231 breast cancer cells was then assessed following exposure to depleted vs. non-depleted lung-conditioned media. Results: Whole populations of all 4 human breast cancer cell lines examined responded via cell line specific patterns of migration towards organ-conditioned media. Notably, all lines demonstrated increased migration towards lung-conditioned media (p<0.05). These observations closely mirror previously observed patterns of in vivo metastatic behavior, providing validation for our ex vivo model system. ALDHhiCD44+ cells responded in a chemotactic manner towards organ-conditioned media in a similar pattern to whole population results. Notably, ALDHhiCD44+ cells showed preferential migration towards lung-conditioned media relative to all other organ-conditioned media tested (p<0.05). Several CD44 ligands including osteopontin (OPN) and E-, L-, and P-selectin were identified by protein array analysis of lung-conditioned media. Immunodepletion of L-selectin or OPN from lung-conditioned media resulted in decreased migration of MDA-MB-231 cells, however only depletion of OPN also resulted in decreased growth relative to non-depleted media. These effects could be abrogated by pre-treatment with a functional CD44 receptor blocking antibody (p<0.05). Conclusions: Our data suggest an important role for CD44 receptor-ligand interactions in mediating lung-specific breast cancer cell migration and growth. To the best of our knowledge, this is the first study to undertake ex vivo investigation of the role of the microenvironment in metastatic organ tropism in the context of the cancer stem cell hypothesis. Citation Format: Ying Xia, Jenny E. Chu, Benjamin Chin-Yee, David Goodale, Alysha K. Croker, Alison L. Allan. Soluble lung-derived factors mediate breast cancer cell migration and growth via CD44 receptor-ligand interactions. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B10.
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) | 0,007 | 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 ».