Breast cancer mammospheres secrete Adrenomedullin to induce lipolysis and browning of adjacent adipocytes.
Adipocytes
/ cytology
Adrenomedullin
/ metabolism
Breast
/ cytology
Breast Neoplasms
/ pathology
Cell Hypoxia
Coculture Techniques
Female
Humans
Lipid Droplets
/ metabolism
Lipolysis
MCF-7 Cells
Paracrine Communication
Spheroids, Cellular
/ metabolism
Tumor Microenvironment
Uncoupling Protein 1
/ metabolism
Adipocytes
Adrenomedullin
Breast cancer
Browning
Lipolysis
UCP1
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
20 Aug 2020
20 Aug 2020
Historique:
received:
21
04
2020
accepted:
09
08
2020
entrez:
22
8
2020
pubmed:
21
8
2020
medline:
15
4
2021
Statut:
epublish
Résumé
Cancer cells cooperate with cells that compose their environment to promote tumor growth and invasion. Among them, adipocytes provide lipids used as a source of energy by cancer cells and adipokines that contribute to tumor expansion. Mechanisms supporting the dynamic interactions between cancer cells and stromal adipocytes, however, remain unclear. We set-up a co-culture model with breast cancer cells grown in 3D as mammospheres and human adipocytes to accurately recapitulate intrinsic features of tumors, such as hypoxia and cancer cell-adipocytes interactions. Herein, we observed that the lipid droplets' size was reduced in adipocytes adjacent to the mammospheres, mimicking adipocyte morphology on histological sections. We showed that the uncoupling protein UCP1 was expressed in adipocytes close to tumor cells on breast cancer histological sections as well as in adipocytes in contact with the mammospheres. Mammospheres produced adrenomedullin (ADM), a multifactorial hypoxia-inducible peptide while ADM receptors were detected in adipocytes. Stimulation of adipocytes with ADM promoted UCP1 expression and increased HSL phosphorylation, which activated lipolysis. Invalidation of ADM in breast cancer cells dramatically reduced UCP1 expression in adipocytes. Breast tumor cells secreted ADM that modified cancer-associated adipocytes through paracrine signaling, leading to metabolic changes and delipidation. Hence, ADM appears to be crucial in controlling the interactions between cancer cells and adipocytes and represents an excellent target to hinder them.
Sections du résumé
BACKGROUND
BACKGROUND
Cancer cells cooperate with cells that compose their environment to promote tumor growth and invasion. Among them, adipocytes provide lipids used as a source of energy by cancer cells and adipokines that contribute to tumor expansion. Mechanisms supporting the dynamic interactions between cancer cells and stromal adipocytes, however, remain unclear.
METHODS
METHODS
We set-up a co-culture model with breast cancer cells grown in 3D as mammospheres and human adipocytes to accurately recapitulate intrinsic features of tumors, such as hypoxia and cancer cell-adipocytes interactions.
RESULTS
RESULTS
Herein, we observed that the lipid droplets' size was reduced in adipocytes adjacent to the mammospheres, mimicking adipocyte morphology on histological sections. We showed that the uncoupling protein UCP1 was expressed in adipocytes close to tumor cells on breast cancer histological sections as well as in adipocytes in contact with the mammospheres. Mammospheres produced adrenomedullin (ADM), a multifactorial hypoxia-inducible peptide while ADM receptors were detected in adipocytes. Stimulation of adipocytes with ADM promoted UCP1 expression and increased HSL phosphorylation, which activated lipolysis. Invalidation of ADM in breast cancer cells dramatically reduced UCP1 expression in adipocytes.
CONCLUSIONS
CONCLUSIONS
Breast tumor cells secreted ADM that modified cancer-associated adipocytes through paracrine signaling, leading to metabolic changes and delipidation. Hence, ADM appears to be crucial in controlling the interactions between cancer cells and adipocytes and represents an excellent target to hinder them.
Identifiants
pubmed: 32819314
doi: 10.1186/s12885-020-07273-7
pii: 10.1186/s12885-020-07273-7
pmc: PMC7441622
doi:
Substances chimiques
ADM protein, human
0
UCP1 protein, human
0
Uncoupling Protein 1
0
Adrenomedullin
148498-78-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
784Subventions
Organisme : Agence Nationale de la Recherche
ID : #ANR-11-LABX-0028-01
Organisme : Agence Nationale de la Recherche
ID : #ANR-18-CE18-006 (hiPS-adipospheres)
Organisme : Association pour la Recherche sur le Cancer
ID : 2016 1204713
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