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

doi:10.1126/science.aaz2193

GSTDTAP > 气候变化

DOI	10.1126/science.aaz2193
	Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis
	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
	2020-07-17
发表期刊	Science
出版年	2020
英文摘要	Metastatic cells display a notable ability to adapt to—and even thrive in—harsh microenvironments. One extreme example is leptomeningeal metastases (LM), cancer cells that enter a region of the central nervous system called the subarachnoid space, which is filled with cerebral spinal fluid (CSF). This anatomic site has a limited supply of micronutrients such as iron, and it harbors immune cells. Chi et al. used single-cell RNA sequencing to study CSF samples from cancer patients with LM (see the Perspective by Garzia and Taylor). They found that LM cells express and use components of a high-affinity iron-capturing system. Through this mechanism, the LM cells avoid the adverse effects of iron deprivation and potentially escape immune attack by limiting the supply of iron to macrophages. Science this issue p. [276][1]; see also p. [250][2] 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. [1]: /lookup/doi/10.1126/science.aaz2193 [2]: /lookup/doi/10.1126/science.abb7041
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/284344
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Yudan Chi,Jan Remsik,Vaidotas Kiseliovas,et al. Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis[J]. Science,2020.
APA	Yudan Chi.,Jan Remsik.,Vaidotas Kiseliovas.,Camille Derderian.,Ugur Sener.,...&Adrienne Boire.(2020).Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis.Science.
MLA	Yudan Chi,et al."Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis".Science (2020).