Table1 Extracellular vesicles as message carriers between pancreatic cancer and stromal cells in tumor microenvironment

PDAC

PSCs

miR-1246 and miR-1290

Stimulate activation and profibrogenic activities in PSCs via activation of ERK and Akt

[57]

PDAC

CAFs

miR-155

Convert normal fibroblasts into CAFs via downregulation of TP53INP1

[71]

PDAC

TAMs

miR-155 and miR-125b-2

MiR-155 & miR-125b transfected PDAC-derived EVs polarized macrophages to M1-like phenotype

[79]

PDAC

TAMs

miR-301a-3p

Induce the M2 polarization of macrophages

[83]

PDAC

Non-polarized macrophages

ICAM-1 and arachidonic acid (AA)

Promote fusion via ICAM-1 and AA carried by exosomes and trigger macrophages to produce pro-tumorigenic factors VEGF, MCP-1, IL-6, IL-1β, MMP-9 and TNF-α

[84]

PDAC

TAMs

Ezrin

Polarize macrophages into a pro-tumor and have a significant impact on the survival of PDAC

[85]

PDAC

DCs

miR-203

Prevent DCs antigen presentation by downregulating TLR4

[97]

PDAC

DCs

miRNA-212-3p

Make DCs unable to activate CD4⁺ T cells

[98]

PDAC

DC

EVs as vaccine together GEM or Sunitinib

Reduce the activation and maturation of MDSC

Suppress tumor cell migration and metastasis

[101]

PDAC

NK

TGF-β1

Suppress NK cell functions and reduce glucose uptake ability

[110]

PDAC

Kupffer cells

MIF

Promote fibronectin secretion and metastasis

[137]

PDAC

Stroma cell

CD151, Tspan8

Promote ECM degradation, reprogram stroma and hematopoietic cells

Engineered PDAC

PDAC resistant to GEM

siRNA for RAB27B mRNA

Decrease exosome secretion and enhanced caspase-3/7 activity leading to apoptosis in GEM-resistant cancer cells

[16]

CAF

PDAC

Lactate, acetate, amino acids, lipids, and TCA cycle intermediates

Reprogram the metabolic machinery and promote tumor growth under nutrient stressed conditions in cancer cells

[60]

CAFs

PDAC

Snail (SNAI1) and its target, microRNA-146a

Promote cancer cells proliferation and gemcitabine resistance

[66]

CAFs

PDAC

miR-106b

Inhibit TP53INP1 gene and increase gemcitabine resistance

[67]

CAFs

PDAC

ANXA6/LRP1/TSP1

Increase aggressiveness

[68]

PSCs

PDAC

miR-5703

Downregulate CMTM4 and activate PI3K/Akt pathway to promote cancer cell proliferation

[49]

PSCs

PDAC

miR‑21

Promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity

[52]

PSCs

PDAC

miR-22

Increase expression of K-Ras and NF-κB and contribute to desmoplastic reaction

[55]

PSCs

PDAC

miR-4465 and miR-616-3p

Promote proliferation and invasion via PTEN repression and AKT activation

[56]

TAMs

PDAC

miR-501-3p

Accelerate the development of PDAC via the activation of the TGF-β

[88]

TAMs

PDAC

miR-365

Enhance the proliferating, migrating and invading potentials of PDAC cells through BTG2/FAK/AKT axis

[89]

TAMs

PDAC

Toll-like receptor 4 (TLR4)

Promote EMT and aggressive behavior in pancreatic cancer cells

[90]

TAMs

PDAC

miR-365

Decrease the sensitivity of PDAC cells to gemcitabine

[91]

TAMs

PDAC

chitinase 3-like-1 (CHI3L1) and fibronectin

Induce PDAC resistance to gemcitabine through extracellular-signal-regulated kinase (ERK) activation

[92]

TAMs

Pancreatic cancer stem cells

miR-21a-5p

Mediate the differentiation and activities of pancreatic cancer stem cells via targeting krüppel-Like Factor 3 (KLF3)

[93]

NK

PDAC

miR-3607-3p

Suppress cancer cells migration and invasion through downregulation of IL-26

[109]

MSCs

PDAC

hsa-miR-143

Promote apoptosis and suppress cell growth, invasion, and migration

[118]

MSCs

PDAC

circ_0030167

Inhibit the invasion, migration, proliferation and stemness of pancreatic cancer cells

[119]

Pancreatic cancer stem cell

Gemcitabine-sensitive pancreatic cells

miR-210

Slow down cell cycle arrest at the G2/M phase, activates mTOR pathway, and induce gemcitabine resistance

[150]