SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway.
J Cell Mol Med
; 28(10): e18397, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38766687
ABSTRACT
Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mice, Knockout
/
Receptors, CXCR4
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MAP Kinase Signaling System
/
Chemokine CXCL12
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Insulinoma
Limits:
Animals
/
Humans
Language:
En
Journal:
J Cell Mol Med
Year:
2024
Document type:
Article