title: Cancer-associated fibroblasts in intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  The aim of this brief review is to provide an up-to-date view of the role played by α-smooth muscle actin-positive cancer-associated fibroblastic cells in promoting intrahepatic cholangiocarcinoma progression.
  
  
  RESULTS
  An increase in α-smooth muscle actin-positive cancer-associated fibroblastic cells in the stroma of intrahepatic cholangiocarcinoma has recently been demonstrated to accelerate cholangiocarcinoma progression. However, our understanding of the evolving cellular and molecular interactions between these stromal cells and cholangiocarcinoma cells in relation to promoting intrahepatic cholangiocarcinoma progression is only just beginning to be elucidated. Imbalances in multifactorial growth factor/cytokine signaling, activation of Hedgehog-GLI signaling and of proteases involved in extracellular matrix remodeling, and matricellular protein-protein and protein-cholangiocarcinoma cell interactions, as well as hypoxia, all appear to factor into the complex and dynamic interactive mechanisms through which cancer-associated fibroblastic cells crosstalk with cholangiocarcinoma cells to promote intrahepatic cholangiocarcinoma progression. Novel three-dimensional organotypic co-culture models are being developed to facilitate relevant studies of cancer-associated fibroblastic cell/cholangiocarcinoma cell interactions that may more accurately mimic physiologically pertinent features of the tumor.
  
  
  CONCLUSIONS
  Increasing our understanding of critical interactive pathways by which cancer-associated fibroblastic cells crosstalk with cholangiocarcinoma cells to promote tumor progression can lead to the development of novel multitargeting strategies for intrahepatic cholangiocarcinoma therapy.
authors.affiliation: Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0297, USA. asirica@mcvh-vcu.edu
authors.forename: Alphonse E
authors.initials: AE
authors.lastname: Sirica
authors.forename: Deanna J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Dumur
mesh_terms: D000199:Actins / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000166:cytology / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D017154:Stromal Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C541116:ACTA2 protein, human; D000199:Actins