Poster Topical Area: Carotenoids and Retinoids
Poster Board Number: 10
Objective: Tumor associated macrophages (TAMs) are critical stromal components intimately involved with the progression, invasion, and metastasis of cancer cells. In response to microenvironmental signals, monocyte-derived macrophages differentiate into M1 (classically activated) like, M2 (alternatively activated) like macrophage (MФ). Dietary carotenoids are essential components of human nutrition and affect a range of physiological functions. The objective of this study is to determine the effects of carotene (β-carotene, lycopene) and xanthophyll (astaxanthin, lutein) on differentiation and polarization of human monocyte-derived MФ.
Methods: Monocyte-to-MФ differentiation was driven by treatment for 6 days with GM-CSF or M-CSF ± individual carotenoids. M1 MФs (+GM-CSF) were activated with LPS + IFNγ; M2 MФs (+M-CSF) were activated with IL-4.
Results: We validated that M1 and M2 cells showed distinct morphologies and expression patterns (qRT-PCR) of scavenger receptors (SR-A, LDLR, CD36, SR-B1) and cytokines (IL-10, IL-12). M1 and M2 markers (CD80, CD163, CD36, CD14 and CD16) and cytokines (PGE2, IL-8, IL-6, IL-10, IL-12, TNFα, IFNγ) were confirmed by flow cytometry. Expression of CD14, CD16, CD163, CD36, and IL-10 was higher in M2 than M1 MФs. Lycopene and astaxanthin decreased SRA, CD36 and LDLR mRNA levels in M1 cells but had no significant effect on M2 cells. Lutein also reduced SRA, CD36 and IL-10 expression in M2. Conversely, β-carotene increased M1 and decreased M2 expression of SRA, CD36, IL-10 and IL-12.
Conclusion: These results show individual carotenoids can regulate MФ scavenger receptor and cytokine expression. We speculate that dietary carotenoids influence TAM polarization, thereby, modulations in TAMs can greatly affect cancer progression and metastasis.
This work was supported, in part, by grants from National Institutes of Health (HD42174 and RR18722)
Texas Tech University Health Sciences Center El Paso
El Paso, Texas