Macrophages Cytokine Spp1 Increases Growth of Prostate Intraepithelial Neoplasia to Promote Prostate Tumor Progression.
3D culture
CD44
Spp1
integrin
macrophage
osteopontin
prostate intraepithelial neoplasia
prostate tumor growth
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
12 Apr 2022
12 Apr 2022
Historique:
received:
17
03
2022
revised:
07
04
2022
accepted:
08
04
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
Prostate cancer development and progression are associated with increased infiltrating macrophages. Prostate cancer is derived from prostatic intraepithelial neoplasia (PIN) lesions. However, the effects macrophages have on PIN progression remain unclear. Here, we showed that the recruited macrophages adjacent to PIN expressed M2 macrophage markers. In addition, high levels of Spp1 transcripts, also known as osteopontin, were identified in these macrophages. Extraneously added Spp1 accelerated PIN cell proliferation through activation of Akt and JNK in a 3D culture setting. We also showed that PIN cells expressed CD44, integrin αv, integrin β1, and integrin β3, all of which have been previously reported as receptors for Spp1. Finally, blockade of Akt and JNK activation through their specific inhibitor completely abolished macrophage Spp1-induced cell proliferation of PIN. Hence, our data revealed Spp1 as another macrophage cytokine/growth factor and its mediated mechanism to upregulate PIN cell growth, thus promoting prostate cancer development.
Identifiants
pubmed: 35457063
pii: ijms23084247
doi: 10.3390/ijms23084247
pmc: PMC9027984
pii:
doi:
Substances chimiques
Cytokines
0
SPP1 protein, human
0
Osteopontin
106441-73-0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIMHD NIH HHS
ID : U54MD007590
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25G06414
Pays : United States
Organisme : NIGMS NIH HHS
ID : T34 GM145508
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD013376
Pays : United States
Organisme : NIMHD NIH HHS
ID : G12 MD007590
Pays : United States
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