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Comparative characterization of the HGF/Met and MSP/Ron systems in primary pancreatic adenocarcinoma

Brett R Vanderwerff1, Kevin J Church2, Leen H Kawas2

  • 1Department of School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.

Cytokine
|June 30, 2019
PubMed

Insights

Hepatocyte growth factor (HGF)/Met signaling drives pancreatic cancer cell proliferation and migration, while macrophage stimulating protein (MSP)/Ron signaling primarily impacts migration, suggesting distinct roles for these receptor tyrosine kinases in pancreatic cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes.
  • Standard chemotherapy offers limited survival benefits for PDAC patients.
  • Receptor tyrosine kinases (RTKs), such as Met and Ron, are implicated in cancer progression and are potential therapeutic targets.

Purpose of the Study:

  • To compare the functional outcomes of the HGF/Met and MSP/Ron signaling pathways in pancreatic cancer.
  • To investigate the in vitro signaling, behavioral, and transcriptomic responses to HGF and MSP in a primary pancreatic adenocarcinoma cell line.
  • To assess the impact of Met and Ron expression on patient survival in pancreatic cancer.

Main Methods:

  • Characterization of signaling, behavioral, and transcriptomic responses to HGF and MSP in vitro.
  • RNA sequencing to analyze transcriptomic alterations.
  • Analysis of clinical data to correlate Met and Ron expression with patient survival.

Main Results:

  • Both HGF and MSP promoted pancreatic cancer cell migration, but only HGF significantly increased proliferation.
  • Transcriptomic analysis revealed that MSP effects partially overlapped with HGF-induced responses.
  • Met expression strongly correlated with patient survival, whereas Ron expression showed limited prognostic value.

Conclusions:

  • The HGF/Met and MSP/Ron pathways exhibit both overlapping and divergent effects on pancreatic cancer cell behavior.
  • The Met pathway appears to be a more significant driver of pancreatic cancer progression and survival than the Ron pathway.
  • Despite differing magnitudes of effect, the MSP/Ron system warrants further investigation for its potential role in pancreatic cancer.
Keywords:
CancerHGFMSPMetPancreaticRon

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