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Background <p>Pancreatic ductal adenocarcinoma (PDAC) is one of the highly lethal malignancies, with no established and effective cure. Therefore, identifying novel molecular targets for this cancer remains an urgent priority.</p> Methods and results <p>We employed a syngeneic orthotopic inoculation model using murine pancreatic cancer Panc02 cells to better recapitulate the pancreatic tumor microenvironment. We established highly metastatic derivatives through three serial transplantation cycles, designated Panc02-3P cells. These cells exhibited enhanced tumorigenicity and metastatic potential both in vitro and in vivo. The RNA-sequence analysis revealed that Panc02-3P cells exhibited mesenchymal-like gene expression changes, compared with parental Panc02 cells, despite no significant changes in EMT-related transcription factor expression. In addition, we found that members of the lysyl oxidase (LOX) family, including LOX, LOXL1, and LOXL3, were markedly upregulated in Panc02-3P cells. The loss-of-function assays using siRNAs targeting LOX and LOXL1 demonstrated that the suppression of these genes significantly attenuated the migratory ability of Panc02-3P cells.</p> Conclusion <p>Collectively, our findings suggest that the LOX family members are associated with the acquisition of a highly migratory and mesenchymal-like phenotype in metastatic pancreatic cancer cells and may contribute to tumor progression.</p>

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In vitro functional analysis of lysyl oxidase family members in highly metastatic pancreatic cancer cells derived from a syngeneic orthotopic model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Kei Takahashi-Yamashiro,
  • Kensuke Miyauchi,
  • Kazuki Shimomura,
  • Mizuki Nishikawa,
  • Yasuyuki Morishita,
  • Masako Nakanishi,
  • Shinya Hayami,
  • Manabu Kawai,
  • Kohei Miyazono,
  • Shogo Ehata

摘要

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly lethal malignancies, with no established and effective cure. Therefore, identifying novel molecular targets for this cancer remains an urgent priority.

Methods and results

We employed a syngeneic orthotopic inoculation model using murine pancreatic cancer Panc02 cells to better recapitulate the pancreatic tumor microenvironment. We established highly metastatic derivatives through three serial transplantation cycles, designated Panc02-3P cells. These cells exhibited enhanced tumorigenicity and metastatic potential both in vitro and in vivo. The RNA-sequence analysis revealed that Panc02-3P cells exhibited mesenchymal-like gene expression changes, compared with parental Panc02 cells, despite no significant changes in EMT-related transcription factor expression. In addition, we found that members of the lysyl oxidase (LOX) family, including LOX, LOXL1, and LOXL3, were markedly upregulated in Panc02-3P cells. The loss-of-function assays using siRNAs targeting LOX and LOXL1 demonstrated that the suppression of these genes significantly attenuated the migratory ability of Panc02-3P cells.

Conclusion

Collectively, our findings suggest that the LOX family members are associated with the acquisition of a highly migratory and mesenchymal-like phenotype in metastatic pancreatic cancer cells and may contribute to tumor progression.