Lactate-Induced CCL8 in Tumor-Associated Macrophages Accelerates the Progression of Colorectal Cancer through the CCL8/CCR5/mTORC1 Axis
Rattachement africain : cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor in promoting immune escape and tumor progression. However, the mechanisms through which LA modulates TAMs in colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify the expression of LA-related genes (LDHA and LAMP2) in CRC tumor tissues and adjacent nontumor tissues (n = 64). The biological effects and mechanisms of LA on macrophages and tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay in vitro, and allograft mouse tumor models in vivo. We found the expression of LDHA and LAMP2 was highly elevated in the tumor regions and positively associated with a poor clinical stage of CRC. A high concentration of LA was generated under hypoxia; it could promote tumor progression and metastasis with the involvement of macrophages. The inhibition of LA release impaired this protumor phenomenon. Mechanically, LA induced M2 macrophages through the AKT/ERK signaling pathway; subsequently, M2 macrophages secreted CCL8 and facilitated the proliferation and metastasis of CRC cells by activating the CCL8/CCR5/mTORC1 axis. This effect was inhibited by the antagonist or knockdown of CCR5. In conclusion, lactate-induced CCL8 in TAMs accelerated CRC proliferation and metastasis through the CCL8/CCR5/mTORC1 axis.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Lactate-Induced CCL8 in Tumor-Associated Macrophages Accelerates the Progression of Colorectal Cancer through the CCL8/CCR5/mTORC1 Axis
- Date Crossref
- 11/12/2023
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Sun Yat-sen University The Seventh Affiliated Hospital pays non établi dans la noticeUniversité ou école supérieure
-
The Seventh Affiliated Hospital of Sun Yat-sen University pays non établi dans la noticeÉtablissement de santé
-
Third Affiliated Hospital of Sun Yat-sen University pays non établi dans la noticeÉtablissement de santé
-
Shantou University Department of General Surgery pays non établi dans la noticeUniversité ou école supérieure
-
First Affiliated Hospital of Shantou University Medical College pays non établi dans la noticeÉtablissement de santé
The Seventh Affiliated Hospital — Sun Yat-sen University, The Seventh Affiliated Hospital of Sun Yat-sen University et Third Affiliated Hospital of Sun Yat-sen University, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.