Dataset Information

Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking.

ABSTRACT: Tumor associated macrophages (TAMs) are associated with tumor growth and metastasis. MRI can detect TAMs labeled with iron oxide (USPIO) or perfluorocarbon (PFC) agents. This study compared these two cell tracking approaches for imaging TAMs in vivo. 4T1 tumors were imaged with MRI at 4 days or 3 weeks post cell implantation after intravenous (i.v.) administration of either USPIO or PFC. Signal loss was detected within tumors at both time points post USPIO. Images acquired at 4 days demonstrated signal loss encompassing the entire tumor and around the periphery at 3 weeks. Number of black voxels suggested higher numbers of TAMs in the tumor at the later time point. After PFC administration, Fluorine-19 (¹⁹F) signal was detected in a similar spatial distribution as signal loss post USPIO. ¹⁹F signal quantification revealed that the number of ¹⁹F spins was not significantly different at the two time points, suggesting a similar number of TAMs were present in tumors but accumulated in different regions. ¹⁹F signal was higher centrally in tumors at 4 days and heterogenous around the periphery at 3 weeks. This study revealed that ¹⁹F-based cell tracking methods better represent TAM density and provides additional information not achievable with iron-based methods.

SUBMITTER: Makela AV

PROVIDER: S-EPMC5296729 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking.

Makela Ashley V AV Gaudet Jeffrey M JM Foster Paula J PJ

Scientific reports 20170208

Tumor associated macrophages (TAMs) are associated with tumor growth and metastasis. MRI can detect TAMs labeled with iron oxide (USPIO) or perfluorocarbon (PFC) agents. This study compared these two cell tracking approaches for imaging TAMs in vivo. 4T1 tumors were imaged with MRI at 4 days or 3 weeks post cell implantation after intravenous (i.v.) administration of either USPIO or PFC. Signal loss was detected within tumors at both time points post USPIO. Images acquired at 4 days demonstrated ...[more]

PMID: 28176853

Similar Datasets

Project description:BackgroundTumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM.MethodsTAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages.ResultsWe revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages.ConclusionsCollectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.

Dataset Information

Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking.

Publications

Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets