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LRP1 regulates GDNF secretion and perineural invasion in pancreatic cancer via PI3K/AKT signaling

Songmei Lou1, Shenhao Liu2, Mengying Zhu3

  • 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, PR China.

Cellular Signalling
|November 11, 2025
PubMed

Insights

Reducing LRP1 in pancreatic cancer cells inhibits perineural invasion (PNI) and nerve growth. This discovery offers new therapeutic targets for managing pancreatic cancer pain and neural invasion.

Area of Science:

  • Oncology
  • Neuroscience
  • Molecular Biology

Background:

  • Pancreatic cancer causes severe pain via cancer cell infiltration into nerves, known as perineural invasion (PNI).
  • Understanding the molecular mechanisms driving PNI is crucial for developing effective pain management strategies.
  • Identifying key molecules involved in PNI can lead to novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of LRP1 (Low-density lipoprotein receptor-related protein 1) in pancreatic cancer perineural invasion.
  • To determine the impact of LRP1 downregulation on the communication between pancreatic cancer cells and neural tissues.
  • To explore LRP1 as a potential therapeutic target for pancreatic cancer-associated pain and neural invasion.

Main Methods:

  • Utilized shRNA lentivirus to downregulate LRP1 expression in pancreatic cancer (Panc-1) and neural (SK-N-SH) cells.
  • Employed an in vitro co-culture model of pancreatic cancer cells with dorsal root ganglia (DRG) to assess synaptic growth.
  • Investigated PNI and neurotrophic factor levels in an animal model of neural invasion.

Main Results:

  • Downregulation of LRP1 suppressed the mutual attraction between pancreatic cancer and neural cells.
  • Reduced LRP1 levels decreased autocrine and paracrine secretion of neurotrophic factors and their receptors.
  • Inhibition of LRP1 significantly reduced DRG growth and perineural invasion, impacting PI3K/AKT and ERK signaling pathways.

Conclusions:

  • LRP1 plays a critical role in mediating the communication between pancreatic cancer cells and surrounding neural tissues.
  • LRP1 downregulation effectively inhibits pancreatic cancer perineural invasion and associated neurotrophic factor signaling.
  • Targeting LRP1 presents a promising therapeutic strategy for pancreatic cancer neural invasion and pain management.
Keywords:
LRP1PNIPancreatic cancerTumor-neural microenvironment

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