Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment

composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2

with tumor-inhibiting or -promoting functions

respectively. We reported that Gremlin 1 (GREM1)

a key pro-fibrogenic factor

is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA

in situ

hybridization

we detected GREM1 mRNA expression within α-smooth muscle actin (SMA)-positive fibroblasts of the pancreatic stroma. These designated Fibroblasts

Grem1+

marginally increased from CP to pancreatic intraepithelial neoplasia (PanIN) and PDAC. Within PDAC

Fibroblasts

Grem1+

increased with higher pathological tumor stages and in a majority of PDAC subtypes screened. Additionally

Fibroblasts

Grem1+

positively correlated with total macrophages (Mac

CD68+

) and M2 macrophages (M2

CD163+

) in PDAC. To begin exploring potential molecular links between Fibroblasts

Grem1+

and macrophages in PDAC

we examined the expression of macrophage migration inhibitory factor (MIF)

an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor. By IHC staining of MIF

we found MIF to be expressed by tumor cells

positively correlated with GREM1; by IHC co-staining

we found MIF to be negatively correlated with M2

CD163+

expression. Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development

and GREM1/MIF may play an important role in macrophage phenotype.