Identification of tumour-reactive lymphatic endothelial cells capable of inducing progression of gastric cancer

Br J Cancer. 2015 Sep 29;113(7):1046-54. doi: 10.1038/bjc.2015.282. Epub 2015 Sep 10.

Abstract

Background: Tumour cells and stromal cells interact in the tumour microenvironment; moreover, stromal cells can acquire abnormalities that contribute to tumour progression. However, interactions between lymphatic endothelial cells (LECs) and tumour cells are largely unexamined. In this study, we aimed to determine whether tumour-specific LECs inhabit the tumour microenvironment and examine their influence on this microenvironment.

Methods: We isolated normal LECs (NLECs) from a non-metastatic lymph node and tumour-associated LECs (TLECs) from cancerous lymph nodes. We examined proliferative and migratory potency, growth factor production, and gene expression of each type of LEC. Moreover, we developed a co-culture system to investigate the interactions between gastric cancer cells and LECs.

Results: When compared with NLEC, TLECs had an abnormal shape, high proliferative and migratory abilities, and elevated expression of genes associated with inflammation, cell growth, and cell migration. NLECs co-cultured with gastric cancer cells from the OCUM12 cell line acquired TLEC-like phenotypes. Also, OCUM12 cells co-cultured with TLECs expressed high levels of genes responsible for metastasis.

Conclusions: Our results demonstrated that LECs interacted with tumour cells and obtained abnormal phenotypes that could have important roles in tumour progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Disease Progression
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Lymph Nodes / cytology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Microenvironment