Leftin Avigdor, Ben-Chetrit Nir, Klemm Florian, Joyce Johanna A, Koutcher Jason A
Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
PLoS One. 2017 Sep 12;12(9):e0184765. doi: 10.1371/journal.pone.0184765. eCollection 2017.
Iron-deposition is a metabolic biomarker of macrophages in both normal and pathological situations, but the presence of iron in tumor and metastasis-associated macrophages is not known. Here we mapped and quantified hemosiderin-laden macrophage (HLM) deposits in murine models of metastatic breast cancer using iron and macrophage histology, and in vivo MRI. Iron MRI detected high-iron pixel clusters in mammary tumors, lung metastasis, and brain metastasis as well as liver and spleen tissue known to contain the HLMs. Iron histology showed these regions to contain clustered macrophages identified by their common iron status and tissue-intrinsic association with other phenotypic macrophage markers. The in vivo MRI and ex vivo histological images were further processed to determine the frequencies and sizes of the iron deposits, and measure the number of HLMs in each deposit to estimate the in vivo MRI sensitivity for these cells. Hemosiderin accumulation is a macrophage biomarker and intrinsic contrast source for cellular MRI associated with the innate function of macrophages in iron metabolism systemically, and in metastatic cancer.
铁沉积是正常和病理情况下巨噬细胞的一种代谢生物标志物，但肿瘤及转移相关巨噬细胞中铁的存在情况尚不清楚。在此，我们利用铁和巨噬细胞组织学以及体内磁共振成像（MRI），对转移性乳腺癌小鼠模型中含铁血黄素负载巨噬细胞（HLM）沉积物进行了定位和定量分析。铁MRI在乳腺肿瘤、肺转移灶、脑转移灶以及已知含有HLM的肝脏和脾脏组织中检测到高铁像素簇。铁组织学显示这些区域含有聚集的巨噬细胞，这些巨噬细胞可通过其共同的铁状态以及与其他表型巨噬细胞标志物的组织固有关联来识别。对体内MRI和体外组织学图像进行进一步处理，以确定铁沉积物的频率和大小，并测量每个沉积物中HLM的数量，从而评估体内MRI对这些细胞的敏感性。含铁血黄素积累是一种巨噬细胞生物标志物和细胞MRI的固有对比源，与巨噬细胞在全身铁代谢系统以及转移性癌症中的固有功能相关。
