Role of VEGF-C and VEGF-D in lymphangiogenesis in gastric cancer.
BACKGROUND
The molecular mechanisms of lymphangiogenesis induced by vascular endothelial growth factor (VEGF)-C and VEGF-D in gastric cancer were studied.


METHODS
VEGF-C and VEGF-D gene expression vectors were transfected into the gastric cancer cell line KKLS, which did not originally express VEGF-C and VEGF-D, and stable transfectants (KKLS/VEGF-C and KKLS/VEGF-D) were established. The cell lines were inoculated into the subserosal layer of the stomach and subcutaneous tissue of nude mice.


RESULTS
VEGF-C and VEGF-D expression in KKLS/VEGF-C and KKLS/VEGF-D cells was found by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Expression of mouse VEGF receptor (VEGFR)-2 and mouse VEGFR-3 mRNA was detected in the KKLS/VEGF-C and KKLS/VEGF-D gastric tumors. Newly formed lymphatic vessels were detected not only in the periphery but also in the center of the tumors. The intratumor lymphatic vessels connected with the preexisting lymphatic vessels in the muscularis mucosa. The average numbers of lymphatic vessels in KKLS/VEGF-C (52.0 +/- 9.5) and KKLS/VEGF-D (16.4 +/- 0.6) gastric tumors were significantly higher than that in the KKLS/control vector tumors (4.0 +/- 1.4).


CONCLUSIONS
VEGF-C and VEGF-D may induce neoformation of lymphatic vessels in experimental gastric tumors by the induction of VEGFR-3 expression.
Yonemura
Yutaka
Y
Gastric Surgery Division, Shizuoka Cancer Center, 1007 Shimo-Nagakubo, Shizuoka 411-8777, Japan. y.yonemura@scchr.jp
Endo
Yoshio
Y
Tabata
Kayoko
K
Kawamura
Taiichi
T
Yun
Hyo-Yung
HY
Bandou
Etsurou
E
Sasaki
Takuma
T
Miura
Masahiro
M
D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014162:Transfection; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism / Q000502:physiology*; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism / Q000502:physiology*
D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D