Regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma

Vascular endothelial growth factor (VEGF)-C and VEGF-D are potent lymphangiogenic factors produced by tumour and stromal cells. The purpose of this study was to investigate the expression of VEGF-C and VEGF-D in the organ microenvironment. We implanted human KM12 colon carcinoma cell lines into the...

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Bibliographic Details
Published in:European journal of cancer (1990) 2004-07, Vol.40 (10), p.1604-1609
Main Authors: Onogawa, Seiji, Kitadai, Yasuhiko, Tanaka, Shinji, Kuwai, Toshio, Kuroda, Tsuyoshi, Chayama, Kazuaki
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line, Tumor
Colonic Neoplasms - metabolism
Colorectal carcinoma
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Lymphangiogenesis
Male
Medical sciences
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Organ microenvironment
Pharmacology. Drug treatments
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
Vascular Endothelial Growth Factor C - metabolism
Vascular Endothelial Growth Factor D - metabolism
VEGF-C
VEGF-D
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Summary:Vascular endothelial growth factor (VEGF)-C and VEGF-D are potent lymphangiogenic factors produced by tumour and stromal cells. The purpose of this study was to investigate the expression of VEGF-C and VEGF-D in the organ microenvironment. We implanted human KM12 colon carcinoma cell lines into the subcutis and caecal wall of nude mice. The expression of VEGF-C and VEGF-D mRNAs and proteins were examined by reverse transcriptase–polymerase chain reaction and immunohistochemistry, respectively. Under culture conditions, VEGF-C mRNA was not detected in KM12 cells; however, VEGF-C expression was detected after implantation of KM12 cells into nude mice. VEGF-C and VEGF-D protein contents were higher in orthotopic (caecal wall) tumours than in ectopic (subcutis) tumours. Small vessels expressing VEGF receptor-3 were observed in the peripheral portions of caecal tumours. In metastatic liver tumours, VEGF-C and VEGF-D proteins were produced in lower amounts than those in caecal tumours. These data suggest that the expression of lymphangiogenic factors is influenced by the organ microenvironment. Therefore, experimental studies of colon cancer lymphangiogenesis should be performed with orthotopic implantation models.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2004.02.026