The recruitment of exogenous endothelial progenitor cells in lung tumor model of nude mice

Chin J Cancer. 2010 Nov;29(11):952-8. doi: 10.5732/cjc.010.10194.

Abstract

Background and objective: Endothelial progenitor cells (EPCs) play an important role in hypoxia-triggered tumor vasculogenesis. However, the homing of exogenous EPCs in tumors is still unclear. In this study, we investigated the recruitment of exogenous EPCs in human lung adenocarcinoma model of nude mice.

Methods: EPCs labeled with green fluorescence protein (GFP) were transplanted into nude mice bearing human lung adenocarcinoma. The growth of tumor was observed. After the mice were killed, GFP-EPCs in different tissues were examined by fluorescence. The tumor tissues were stained for CD133, hypoxia-inducible factor-1alpha (HIF-1α), stromal cell-derived factor-1α (SDF-1α), and vascular endothelial growth factor receptor (KDR). Real-time polymerase chain reaction of CD133, HIF-1α, SDF-1α, and VEGF-1 were also performed.

Results: The growth of tumor in EPC group was significantly faster than that in saline solution group (P <0.05). Under fluorescence microscope, GFP-EPCs were strongly expressed in both tumor and bone marrow. EPCs were recruited to the tumor periphery to participate in tumor vasculogenesis. The expression of CD133, HIF-1α, and SDF-1 mRNA in tumor and bone marrow were significantly higher than that in the liver, spleen, and skin (P<0.05).

Conclusions: Exogenous EPCs can be recruited to tumor and accelerate tumor growth. Except tumor, bone marrow can also recruit EPCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Bone Marrow / metabolism
  • Bone Marrow / pathology*
  • Cell Line, Tumor
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Endothelial Cells / pathology
  • Endothelial Cells / transplantation*
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Peptides / genetics
  • Peptides / metabolism
  • RNA, Messenger / metabolism
  • Stem Cell Transplantation*
  • Stem Cells / pathology*
  • Transfection
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Chemokine CXCL12
  • Glycoproteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Green Fluorescent Proteins