Abstract 2843: Tumor macrophages utilize ATF3 to promote breast cancer metastasis
Notice bibliographique
Résumé
Abstract Objective: Cancer progression is facilitated by a complex network of interactions between cancer cells and host-derived components, such as stromal cells and extracellular matrix in the tumor microenvironment. We sought to identify the factors that mediate these dynamic cancer-host interplays. Specifically, we asked how the host responds to signals from the cancer cells. To this end, we investigated the role of ATF3, an adaptive-response gene in the cellular stress response network. Overwhelming evidence indicates that ATF3 is induced by a broad spectrum of extra- and intra-cellular signals in a variety of cell types. As such, it is as an excellent candidate for mediating host responses to cancer cells. Methods: We injected breast cancer cells (MMTV-PyMT cells) into syngeneic wild type (WT) or ATF3 knockout (KO) mice, performed survival surgery to remove the primary tumors, and examined metastasis two months after tumor removal. Results: We found that ATF3 deficiency in the host did not affect primary tumor formation; excitingly, though, it dramatically decreased lung metastasis. Analyses of the circulating tumor cells and lung colonization indicated that both early and late steps in the metastatic cascade were defective in the KO host. Since soluble factors are an integral part of the mechanisms by which the host transmits systemic responses, we analyzed the plasma of normal and tumor-bearing mice by an antibody array. Intriguingly, plasma from tumor-bearing KO mice demonstrated a marked impairment in the abundance of various molecules that are known to play important roles in metastasis, suggesting that ATF3 in the host promotes a systemic environment that enhances cancer metastasis. Since the KO mice are whole body KO, the results above do not indicate the cell type(s) in which ATF3 is playing this critical role. We will present evidence that ATF3 plays an important role, at least in part, in the tumor associated macrophages (TAMs), where it up-regulates MMP9 as a functionally important target gene. Two lines of evidence indicated that our findings on ATF3 have clinical relevance. First, analyses of human tumor microarrays by immunohistochemistry revealed that ATF3 expression in monocytic cells correlated with poor outcome. Second, analyses of the mouse TAMs from the WT and KO host identified ∼400 ATF3-regulated genes. Among these genes, a 60-gene signature was identified that could distinguish the human breast tumor stroma from the normal breast stroma (McGill Breast Stroma dataset). Significantly, this signature predicted outcome in two independent patient cohorts. Conclusion and Significance: We uncovered a previously unknown role for ATF3: it is induced in the host during cancer development and its expression in the host cells, specifically the TAMs, promotes metastasis. This finding is significant because it not only links host stress response to cancer metastasis, it also identified a new gene signature that predicts outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2843. doi:10.1158/1538-7445.AM2011-2843
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 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) | 0,002 | 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 tête enseignante, 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 ».