| First Author | Tiwari P | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 6 | Pages | 1345-1358 |
| PubMed ID | 31053611 | Mgi Jnum | J:279077 |
| Mgi Id | MGI:6315124 | Doi | 10.1084/jem.20181616 |
| Citation | Tiwari P, et al. (2019) Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer. J Exp Med 216(6):1345-1358 |
| abstractText | Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)-dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity. |
