The chemotactic interaction between CCL21 and its receptor, CCR7, facilitates the progression of pancreatic cancer via induction of angiogenesis and lymphangiogenesis

J Hepatobiliary Pancreat Sci. 2011 Nov;18(6):821-8. doi: 10.1007/s00534-011-0395-4.

Abstract

Background: In this study, we report the influence of CCL21 and its receptor, CCR7, on the progression of pancreatic cancer and illuminates the correlation between the CCL21/CCR7 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC).

Methods: A total of 30 patients with pancreatic cancer was involved in the current study. The expression of CCL21 and CCR7 in cancerous tissues, paracancerous tissues and normal pancreas were investigated using real-time PCR, Western blot and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry.

Results: Compared to paracancerous tissues and normal pancreas, CCL21 expression in cancerous tissues was detected at a significantly low level. In contrast, the CCR7 expression was considerably higher in cancerous tissues than in normal pancreas and paracancerous tissues. Additionally, a significant correlation between the expression pattern of the CCL21/CCR7 axis and clinicopathological features, such as lymph node metastasis, was identified. Furthermore, we found that CCL21 expression was significantly associated with MVD but not significantly associated with MLVD, while CCR7 expression was significantly associated with MLVD but not significantly associated with MVD.

Conclusions: The chemotactic interaction between CCR7 and its ligand, CCL21, may be a critical event during progression in pancreatic cancer, and its underlying mechanism may be induction of angiogenesis and lymphangiogenesis regulated by this chemotactic interaction.

Keywords: angiogenesis; chemokine receptors; chemokines; lymphangiogenesis; pancreatic neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Cell Line, Tumor
  • Chemokine CCL21 / biosynthesis
  • Chemokine CCL21 / genetics*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphangiogenesis / genetics*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • RNA, Neoplasm / genetics*
  • Real-Time Polymerase Chain Reaction
  • Receptors, CCR7 / biosynthesis
  • Receptors, CCR7 / genetics*
  • Retrospective Studies

Substances

  • CCL21 protein, human
  • CCR7 protein, human
  • Chemokine CCL21
  • RNA, Neoplasm
  • Receptors, CCR7