The role of KDR in the interactions between human gastric carcinoma cell and vascular endothelial cell

World J Gastroenterol. 2002 Aug;8(4):596-601. doi: 10.3748/wjg.v8.i4.596.

Abstract

Aim: To study the interactions between human gastric carcinoma cell (HGCC) and human vascular endothelial cell (HVEC), and the role of KDR in these interactions.

Methods: Antisense oligodexynucleotide(ASODN) specific to KDR gene was devised and added to the culture medium of HGCC and HVEC. After the action of ASODN, the proliferation of two cells was measured by MTT method. The role of KDR in regulating the proliferation of two kinds of cells was known through observing the effect of ASODN on them. The conditioned mediums (CMs) of HGCC and HVEC were prepared. The CM of one kind of cell was added acting on the other kind of cell, then the cell proliferation was measured by MTT. After the action of ASODN or CM, the cellular expression of KDR gene was detected with in situ hybridization (ISH) for mRNA level and with immunohistochemical staining for protein level. ABC -ELISA was used to detect hVEGF in the CMs of two cells.

Results: KDR ASODN could specifically inhibit the proliferation of HGCC and HVEC significantly. The growth inhibitory rate amounted to 55.35 % and 54.83 %, respectively (P<0.01). HGCC and HVEC could secret a certain level of hVEGF(92.06+/-1.69 ng/L, 77.70+/-8.04 ng/L). The CM of HGCC could significantly stimulate the growth(2.70+/-0.01 times) and KDR gene expression of HVEC(P<0.01) while the CM of HVEC could significantly inhibit the growth(52.97+/-0.01 %) and KDR gene expression of HGCC (P<0.01).

Conclusion: KDR plays a key role in regulating the proliferation of HGCC and HVEC. There exist complicated interactions between HGCC and HVEC. HGCC can significantly stimulate the growth of HVEC while HVEC can significantly inhibit the growth of HGCC. KDR is involved in the interactions between them.

MeSH terms

  • Cell Communication
  • Cell Division / drug effects
  • Cell Line
  • Culture Media, Conditioned
  • Endothelial Growth Factors / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Gene Expression
  • Humans
  • Lymphokines / metabolism
  • Neovascularization, Pathologic
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptors, Growth Factor / genetics*
  • Receptors, Vascular Endothelial Growth Factor
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Culture Media, Conditioned
  • Endothelial Growth Factors
  • Lymphokines
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor