Open AccessDownregulation of MMP1 functions in preventing perineural invasion of pancreatic cancer through blocking the NT ‐3/ TrkC signaling pathway
Author(s) -
Xu Xiaoqing,
Lu Xiaomin,
Chen Liping,
Peng Ke,
Ji Fuhai
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24719
Subject(s) - mmp1 , gene knockdown , cancer research , chemistry , perineural invasion , microbiology and biotechnology , biology , apoptosis , medicine , cancer , biochemistry , gene expression , gene
Abstract Background Pancreatic cancer (PC) is a fatal malignancy that frequently involves perineural invasion (PNI). This study aims to investigate the function and underlying mechanisms of matrix metalloproteinase‐1 (MMP1) in PNI of PC. Methods Human pancreatic cancer PANC‐1 cells were co‐cultured with dorsal root ganglion in vitro. The expression of MMP1, epithelial–mesenchymal transition (EMT) markers, Schwann cell markers, neurotrophic factors, NT‐3, and TrkC was measured by qRT‐PCR or Western blot. Transwell assay was performed to evaluate cell migration and invasion. In vivo model of PNI was established via inoculating PANC‐1 cells into mice. PANC‐1 cells and mice were also treated with LM22B‐10 (an activator of TrkC) to confirm the mechanisms involving NT‐3/TrkC in PNI of PC both in vivo and in vitro. Results The expression of MMP1 was significantly higher in PDAC tissues than non‐cancerous tissues, which was positively associated with PNI. MMP1 knockdown repressed the migration and invasion of PANC‐1 cells. Except for E‐cadherin, the expression of EMT markers, Schwann cell markers, neurotrophic factors, NT‐3, and TrkC was inhibited by MMP1 silencing. The same effects of MMP1 knockdown on the above factors were also observed in the PNI model. Moreover, MMP1 knockdown elevated the sciatic nerve function and reduced PNI in the model mice. LM22B‐10 partially abolished the effects of MMP1 knockdown both in vivo and in vitro. Conclusions Silencing of MMP1 prevents PC cells from EMT and Schwann‐like cell differentiation via inhibiting the activation of the NT‐3/TrkC signaling pathway, thus alleviating the PNI of PC.