Table 1.

Biological comparison of quiescent PSCs (qPSCs) and activated PSCs (aPSCs)

	Biological behaviors or functions	Specific/selective biomarkers
qPSCs	-Store retinoids in droplets [13, 17] -Function as an immune, progenitor and intermediary cell [16] -Stimulate amylase secretion, phagocytosis and immunity [16] -Secrete MMPs and TIMPs to maintain ECM turnover; prevent collagens deposition [17] -Produce cytokines, growth factors; basic exo/endocrine secretions in a proper way [18] -May contribute to acinar regeneration [18] -Involve in maintenance of pancreatic tissue architecture [16, 18] -Help to sustain homeostasis in pancreas microenvironment [16]	desmin [15, 16] nestin [15, 16] vimentin [18] synemin [15, 16] GFAP [15, 16] NGF [15, 16]
aPSCs	-Induce desmoplastic reactions in TME [19], elevate interstitial pressure [22] -Induce hypovascularity and produce excess ECM [19, 23] -Contribute to hypoxic and low-nutrient conditions [77, 79] -Lose vitamin A lipid vacuoles [18] -Develop spindle-shaped morphology [17, 18] -Generate growth factors (GFs), cytokines, exosomes, micRNAs that enhance tumor survival, proliferation, migration and metastasis [34, 73, 84, 85] -Promote angiogenesis, PNI and EMT [44, 45, 54, 61] -Mediate chemoresistance and radioresistance [70, 105] -Contribute to complex metabolic networks in TME [112, 115] -Interact with PDA cells or other stromal components [47] -Contribute to immunosuppressive regulations and immune evasion [130–133]	α-SMA [17, 18] FAP-α [19] FSP-1 [17–19] Fibrinogen [18, 19]

Notes: Biological behaviors and functions dramatically change during phenotypic transition of PSCs. Biomarkers of qPSCs are not specific.

Abbreviations: aPSCs activated pancreatic stellate cells, qPSCs quiescent pancreatic stellate cells, GFs growth factors, PNI perineural invasion, EMT Epithelial-Mesenchymal Transition, TME tumor microenvironment, GFAP glial fibrillary acidic protein, α-SMA α-smooth muscle actin, NGF nerve growth factor, FAP-α fibroblast activation protein-α, FSP-1 fibroblast-specific protein-1