Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer

British Journal of Cancer
Srinivasa P PothulaMinoti V Apte

Abstract

Pancreatic stellate cells (PSCs, which produce the stroma of pancreatic cancer (PC)) interact with cancer cells to facilitate PC growth. A candidate growth factor pathway that may mediate this interaction is the HGF-c-MET pathway. Effects of HGF inhibition (using a neutralising antibody AMG102) alone or in combination with gemcitabine were assessed (i) in vivo using an orthotopic model of PC, and (ii) in vitro using cultured PC cells (AsPC-1) and human PSCs. We have shown that human PSCs (hPSCs) secrete HGF but do not express the receptor c-MET, which is present predominantly on cancer cells. HGF inhibition was as effective as standard chemotherapy in inhibiting local tumour growth but was significantly more effective than gemcitabine in reducing tumour angiogenesis and metastasis. HGF inhibition has resulted in reduced metastasis; however, interestingly this antimetastatic effect was lost when combined with gemcitabine. This suggests that gemcitabine treatment selects out a subpopulation of cancer cells with increased epithelial-mesenchymal transition (EMT) and stem-cell characteristics, as supported by our findings of increased expression of EMT and stem-cell markers in tumour sections from our animal model. In vitro studies ...Continue Reading

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Citations

May 18, 2016·Nature Reviews. Gastroenterology & Hepatology·Minoti V Apte, Jeremy S Wilson
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Dec 5, 2020·International Journal of Molecular Sciences·Srinivasa P PothulaMinoti V Apte
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Methods Mentioned

BETA
PCR
Protein Assay
ELISA
transgenic

Software Mentioned

GraphPad
GraphPad Prism

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