美国斯隆·凯特琳纪念癌症中心Adrienne Boire研究组发现癌细胞利用lipocalin-2收集软脑膜转移中的微量铁。2020年7月17日，《科学》杂志发表了这一成果。

为了研究这些轻脑膜转移瘤（LM）中的癌细胞克服限制的机制，他们对五名LM患者的脑脊液（CSF）进行了单细胞RNA测序。他们发现，CSF中的癌细胞而非巨噬细胞表达了铁结合蛋白lipocalin-2（LCN2）及其受体SCL22A17。这些巨噬细胞产生炎性细胞因子，诱导癌细胞LCN2表达，但自身不产生LCN2。在LM小鼠模型中，LCN2 / SLC22A17系统供给癌细胞生长，并受到铁螯合抑制。因此，癌细胞似乎通过与巨噬细胞竞争铁而存活在CSF中。

据了解，肿瘤微环境在癌症进展中，尤其是在中枢神经系统转移中，起着至关重要的调节作用。CSF充填的软脑膜内的癌细胞面临着巨大的微环境挑战，包括炎症和稀少的微量营养素。

附：英文原文

Title: Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis

Author: Yudan Chi, Jan Remsik, Vaidotas Kiseliovas, Camille Derderian, Ugur Sener, Majdi Alghader, Fadi Saadeh, Katie Nikishina, Tejus Bale, Christine Iacobuzio-Donahue, Tiffany Thomas, Dana Pe’er, Linas Mazutis, Adrienne Boire

Issue&Volume: 2020/07/17

Abstract: The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)–filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. Thus, cancer cells appear to survive in the CSF by outcompeting macrophages for iron.

DOI: 10.1126/science.aaz2193

Source: https://science.sciencemag.org/content/369/6501/276