Highly lymphatic metastatic pancreatic cancer cells possess stem cell-like properties

Int J Oncol. 2013 Mar;42(3):979-84. doi: 10.3892/ijo.2013.1780. Epub 2013 Jan 18.

Abstract

Cancer stem cells are thought to be the origin of tumor metastasis. However, evidence of cancer stem cells as the source of lymphatic metastasis in pancreatic cancer is not clear. In this study, we examined the stem cell-like properties of the highly lymphatic metastatic pancreatic cancer cells BxPC-3-LN. Compared with the parental BxPC-3 cells, the BxPC-3-LN cells showed stem cell-like properties, including high lymphatic metastasis potential, self-renewal ability and chemoresistance. In addition, the BxPC-3-LN cells also expressed higher levels of sonic hedgehog and migrating cancer stem cell surface markers (CD133 and CXCR4) compared to the parental BxPC-3 cells. The growth of BxPC-3-LN cells was significantly inhibited by gemcitabine combined with the sonic hedgehog inhibitor cyclopamine. The BxPC-3-LN cells expressed lower levels of let-7, miR-34, miR-107, miR-125, miR-128, miR-130, miR-132 and miR-141 than the parental BxPC-3 cells detected by microRNA PCR array, which were reported to have close relation to stem cell factors. This study provides evidence that cancer stem cells are the major sources of pancreatic cancer lymphatic metastasis, and microRNAs may regulate lymphatic metastasis in pancreatic cancer through modulating cancer stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / biosynthesis
  • Antimetabolites, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Gemcitabine
  • Glycoproteins / biosynthesis
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / biosynthesis
  • Humans
  • Lymphatic Metastasis*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism*
  • Peptides
  • Receptors, CXCR4 / biosynthesis
  • Veratrum Alkaloids / pharmacology

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antimetabolites, Antineoplastic
  • CXCR4 protein, human
  • Glycoproteins
  • Hedgehog Proteins
  • MicroRNAs
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Receptors, CXCR4
  • SHH protein, human
  • Veratrum Alkaloids
  • Deoxycytidine
  • cyclopamine
  • Gemcitabine