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. Author manuscript; available in PMC: 2018 Jan 24.
Published in final edited form as: Annu Rev Pathol. 2016 Dec 5;12:153–186. doi: 10.1146/annurev-pathol-052016-100322

Table 2.

Mechanisms by which HSC/CAF promote CCA growth

Mediator Effects on tumor Mechanisms Ref
Promotion of proliferation and invasion Periostin Promotion of tumor cell proliferation and invasion, chemoresistance and metastasis. Contributes to fibrogenesis and desmoplasia. Interaction with integrins α5β1 orα6β4 and subsequent activation of AKT and FAK, thereby promoting migration. (202; 211; 212; 242; 245)
Thrombospondin-1 Promotion of CCA invasion and metastasis. Correlates with hypovascularity of iCCA. Activation of plasminogen/plasmin system and via upregulation of metalloproteinases. (247; 248)
HGF Proliferation and possibly invasion in vitro Activation of HGF receptor c-Met promotes CCA proliferation; HGF pregulation of CXCR4 expression in CCA cells (211)
Tenascin-c Tnc expression at the invasive front correlates with poor prognosis. Not well investigated. Interacts with periostin. Tnc promotes survival and stemness in other tumors. (215)
CXCL12 iCCA progression and invasion. MEK1/2, AKT activation in vitro and via activationof the canonical Wnt signaling pathway in vivo. (255–257)
MMP2, MMP9 Promotion of tumor progression and invasion. ECM proteins degradation (216; 218)
Promotion of survival PDGF-BB Promotion of tumor cell survival. PDGF-BB protects from TRAIL-induced apoposis through hedgehog-mediated signals. (220)
Modulation of immune response IL-1β Enhancement of tumor cell migration and invasion via CXCL5. IL-1β from HSC induces Cxcl5 in tumor cells, thereby enhancing tumor cells migration and invasion. (260)