Abstract 5894: Stromal fibroblasts from metastatic breast cancer promote proliferation and migration of breast cancer cell and regulate its stemness
Notice bibliographique
Résumé
Abstract Breast cancer is one of the most common causes of cancer-related death in women in the world. Although most research is focused on the tumor cells, it is important to elucidate the molecular nature of the tumor-stromal relationship to truly understand the biology of breast tumor growth. Cancer-associated fibroblasts (CAFs) are the major cellular constituents in the tumor microenvironment. CAFs are in direct contact with the adjacent cancer cells and crosstalk with them through soluble cytokines, growth factors and exosomes during carcinogenesis in human breast cancer. To determine for the first time the function of CAFs in metastatic sites of breast cancer, we collected CAFs from human patients of metastatic sites (m-CAFs) and compared them with CAFs from primary tumor (p-CAFs) and normal fibroblasts (NFs). We found that m-CAFs expressed higher levels of α-smooth muscle actin (SMA) compared with p-CAFs and NFs. The proliferation of MDA-MB-436 breast cancer cells was significantly increased by treatment with conditioned medium (CM) from m-CAFs compared with p-CAFs in vitro. Also, CM by m-CAFs induced paclitaxel resistance in MDA-MB-436 cells, suggesting that soluble factors produced by m-CAFs promote chemo-resistance, to a greater extent than CM from p-CAFs. The migration and invasion ability of MDA-MB-436 cells co-cultured with m-CAFs CM was significantly greater than that of the p-CAFs CM. m-CAFs outperformed the p-CAFs and NFs in terms of their ability to promote sphere-forming activity in a 3D in vitro culture model. Furthermore, m-CAFs protected MDA-MB-436 cells from the cytotoxic effects of doxorubicin more than p-CAFs in this spheroid 3-D culture. When MDA-MB-436 cells were sorted from these spheroids and grew in the respective CMs, they showed higher expression of the stemness markers of CD44+CD24- compared with cells obtained from p-CAFs/MDA-MB-436 spheroids. Also these cells from the co-culture with m-CAFs experienced with the cadherin switch. Nanog has been demonstrated to promote chemoresistant and epithelial-mesenchymal transition (EMT). The results displayed that MDA-MB-436 cells incubated with the CM from the m-CAFs had a higher expression of Nanog compared with that of p-CAFs. RNA-seq results showed that IGF2 is one of the most different genes between m-CAFs and p-CAFs, its expression was more significant in m-CAFs co-cultured with MDA-MB-436 cells than p-CAFs. The signaling pathway in MDA-MB-436 cells were comparable between co-cultured with m-CAFs CM and the IGF2 stimulation at 2 hours. All these data illustrates that fibroblasts isolated from metastatic site differed in terms of their ability to promote breast cancer cells progression compared to p-CAFs. Our data suggests that m-CAFs are more potent than p-CAFs in inducing the proliferation, migration, drug resistance and cancer stemness of breast cancer cells in an in vitro model. Citation Format: Yirui Gui, Adriana Aguilar-Mahecha, Marguerite Buchanan, Mark Basik. Stromal fibroblasts from metastatic breast cancer promote proliferation and migration of breast cancer cell and regulate its stemness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5894. doi:10.1158/1538-7445.AM2017-5894
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 | 0,001 |
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 ».