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2017 ; 5
(ä): 9
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gab.com Text
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English Wikipedia
Metabolomics guided pathway analysis reveals link between cancer metastasis,
cholesterol sulfate, and phospholipids
#MMPMID29093815
Johnson CH
; Santidrian AF
; LeBoeuf SE
; Kurczy ME
; Rattray NJW
; Rattray Z
; Warth B
; Ritland M
; Hoang LT
; Loriot C
; Higa J
; Hansen JE
; Felding BH
; Siuzdak G
Cancer Metab
2017[]; 5
(ä): 9
PMID29093815
show ga
BACKGROUND: Cancer cells that enter the metastatic cascade require traits that
allow them to survive within the circulation and colonize distant organ sites. As
disseminating cancer cells adapt to their changing microenvironments, they also
modify their metabolism and metabolite production. METHODS: A mouse xenograft
model of spontaneous tumor metastasis was used to determine the metabolic
rewiring that occurs between primary cancers and their metastases. An
"autonomous" mass spectrometry-based untargeted metabolomic workflow with
integrative metabolic pathway analysis revealed a number of differentially
regulated metabolites in primary mammary fat pad (MFP) tumors compared to
microdissected paired lung metastases. The study was further extended to analyze
metabolites in paired normal tissues which determined the potential influence of
metabolites from the microenvironment. RESULTS: Metabolomic analysis revealed
that multiple metabolites were increased in metastases, including cholesterol
sulfate and phospholipids (phosphatidylglycerols and phosphatidylethanolamine).
Metabolite analysis of normal lung tissue in the mouse model also revealed
increased levels of these metabolites compared to tissues from normal MFP and
primary MFP tumors, indicating potential extracellular uptake by cancer cells in
lung metastases. These results indicate a potential functional importance of
cholesterol sulfate and phospholipids in propagating metastasis. In addition,
metabolites involved in DNA/RNA synthesis and the TCA cycle were decreased in
lung metastases compared to primary MFP tumors. CONCLUSIONS: Using an integrated
metabolomic workflow, this study identified a link between cholesterol sulfate
and phospholipids, metabolic characteristics of the metastatic niche, and the
capacity of tumor cells to colonize distant sites.