title: MALDI-TOF MS imaging of metabolites with a N-(1-naphthyl) ethylenediamine dihydrochloride matrix and its application to colorectal cancer liver metastasis.
abstract: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a label-free technique for identifying multiplex metabolites and determining both their distribution and relative abundance in situ. Our previous study showed that N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC) could act as a matrix for laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) detection of oligosaccharides in solution. In the present study, NEDC-assisted LDI-TOF MSI yielded many more endogenous compound peaks between m/z 60 and m/z 1600 than 9-aminoacridine (9-AA). Our results show that NEDC-assisted LDI-TOF MSI is especially well-suited for examining distributions of glycerophospholipids (GPs) in addition to low molecular weight metabolites below m/z 400. Particularly, NEDC matrix allowed the LDI-TOF MSI of glucose in animal tissue. Furthermore, NEDC-assisted LDI-TOF MSI was applied to a mouse model of colorectal cancer liver metastasis. We revealed the distinct spatio-molecular signatures of many detected compounds in tumor or tumor-bearing liver, and we found that taurine, glucose, and some GPs decreased in tumor-bearing liver as the tumor developed in liver. Importantly, we also found a glucose gradient in metastatic tumor foci for the first time, which further confirms the energy competition between tumors and liver remnant due to the Warburg effect. Our results suggest that NEDC-assisted LDI MSI provides an in situ label-free analysis of multiple glycerophospholipids and low molecular weight metabolites (including glucose) with abundant peaks and high spatial resolution. This will allow future application to in situ definition of biomarkers, signaling pathways, and disease mechanisms.
authors.affiliation: Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Shulan
authors.initials: S
authors.lastname: Qiu
authors.forename: Suming
authors.initials: S
authors.lastname: Chen
authors.forename: Caiqiao
authors.initials: C
authors.lastname: Xiong
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.forename: Jiyun
authors.initials: J
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.forename: Zongxiu
authors.initials: Z
authors.lastname: Nie
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003952:Diagnostic Imaging; D005029:Ethylenediamines / Q000737:chemistry*; D005947:Glucose / Q000032:analysis*; D007091:Image Processing, Computer-Assisted; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D005029:Ethylenediamines; C008588:N-(1-naphthyl)ethylenediamine; D005947:Glucose