Exploring Metabolic Adaptations to the Acidic Microenvironment of Osteosarcoma Cells Unveils Sphingosine 1-Phosphate as a Valuable Therapeutic Target.
FTY720
acidity
lipidomics
osteosarcoma
sphingolipid
sphingosine 1-phosphate
tumor microenvironment
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
15 Jan 2021
15 Jan 2021
Historique:
received:
30
11
2020
revised:
04
01
2021
accepted:
11
01
2021
entrez:
20
1
2021
pubmed:
21
1
2021
medline:
21
1
2021
Statut:
epublish
Résumé
Acidity is a key player in cancer progression, modelling a microenvironment that prevents immune surveillance and enhances invasiveness, survival, and drug resistance. Here, we demonstrated in spheroids from osteosarcoma cell lines that the exposure to acidosis remarkably caused intracellular lipid droplets accumulation. Lipid accumulation was also detected in sarcoma tissues in close proximity to tumor area that express the acid-related biomarker LAMP2. Acid-induced lipid droplets-accumulation was not functional to a higher energetic request, but rather to cell survival. As a mechanism, we found increased levels of sphingomyelin and secretion of the sphingosine 1-phosphate, and the activation of the associated sphingolipid pathway and the non-canonical NF-ĸB pathway, respectively. Moreover, decreasing sphingosine 1-phosphate levels (S1P) by FTY720 (Fingolimod) impaired acid-induced tumor survival and migration. As a confirmation of the role of S1P in osteosarcoma, we found S1P high circulating levels (30.8 ± 2.5 nmol/mL,
Identifiants
pubmed: 33467731
pii: cancers13020311
doi: 10.3390/cancers13020311
pmc: PMC7830496
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 21403
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