Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases). Furthermore, these factors are long-term stored within an abnormally remodeled extracellular matrix (ECM), which in turn can deleteriously mold cancer cell behavior. In this review, we will highlight evidence for the active role played by reactive stromal cells (as well as by the TRS-associated ECM) in CCA progression, including an overview of the most relevant TRS-derived signals possibly fueling CCA cell aggressiveness. Hopefully, a deeper knowledge of the paracrine communications reciprocally exchanged between cancer and stromal cells will steer the development of innovative, combinatorial therapies, which can finally hinder the progression of CCA, as well as of other cancer types with abundant TRS, such as pancreatic and breast carcinomas

Brivio, S., Cadamuro, M., Strazzabosco, M., Fabris, L. (2017). Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness. WORLD JOURNAL OF HEPATOLOGY, 9(9), 455-468 [10.4254/wjh.v9.i9.455].

Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness

BRIVIO, SIMONE
Primo
;
CADAMURO, MASSIMILIANO
Secondo
;
STRAZZABOSCO, MARIO
Penultimo
;
2017

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases). Furthermore, these factors are long-term stored within an abnormally remodeled extracellular matrix (ECM), which in turn can deleteriously mold cancer cell behavior. In this review, we will highlight evidence for the active role played by reactive stromal cells (as well as by the TRS-associated ECM) in CCA progression, including an overview of the most relevant TRS-derived signals possibly fueling CCA cell aggressiveness. Hopefully, a deeper knowledge of the paracrine communications reciprocally exchanged between cancer and stromal cells will steer the development of innovative, combinatorial therapies, which can finally hinder the progression of CCA, as well as of other cancer types with abundant TRS, such as pancreatic and breast carcinomas
Articolo in rivista - Review Essay
Desmoplasia; cancer-associated fibroblast; Inflammation; Lymphatic endothelial cell; Mesenchymal stem cellExtracellular matrix; Tumor microenvironment; Tumor-associated macrophage; Hepatology
English
28-mar-2017
2017
9
9
455
468
none
Brivio, S., Cadamuro, M., Strazzabosco, M., Fabris, L. (2017). Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness. WORLD JOURNAL OF HEPATOLOGY, 9(9), 455-468 [10.4254/wjh.v9.i9.455].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/151676
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