[Correlation of angiogenesis with expression of vascular endothelial growth factor and its receptors in lung carcinoma].
OBJECTIVE
In order to search new therapeutic strategies, study the relationship between angiogenesis and vascular endothelial growth factor and its two receptors in lung carcinoma.


METHODS
The study consisted of 49 patients with lung carcinoma treated with curative surgery. Immunohistochemistry on paraffin sections was performed with anti-human factor VIII antibody to study the microvascular density (MVD), and with antibodies to VEGF, Flt1, and KDR to investigate the expression of these three proteins in different cellular compartments. The survival time was compared between low MVD and high MVD groups by the Kaplan-Meier method.


RESULTS
(1) Expression of VEGF and its two receptors in tumor cells, stromal fibroblasts and endothelial cells was demonstrated. (2) There was no significant difference between low MVD and high MVD groups in the clinical data, including TNM stage, clinical phase, pathologic type, and tumor cell differentiation (P > 0.05). Survival analysis showed that the high MVD group was associated with a high risk of death. (3) There was no significant difference between low MVD and high MVD groups in VEGF expression in tumor cells, but in endothelial cells both Flt1 and KDR were correlated with high microvessel count. (4) The high expression of VEGF in tumor cells was correlated with that in stromal fibroblasts. The level of expression in both cells was consistent. (5) In both tumor cells and endothelial cells, high co-expression of VEGF and KDR was consistent, but that of VEGF and Flt1 showed inconsistency.


CONCLUSIONS
(1) Not or rarely affected by clinical factors, MVD is a good and independent prognostic factor for patients with lung carcinoma. (2) The angiogenesis is induced not only by VEGF itself, but via VEGF receptors too. VEGF and its receptors thus appear to be new therapeutic targets for lung carcinoma. (3) VEGF appears to be produced by both tumor cells and stromal fibroblasts. (4) The result suggests that tumor expansion and angiogenesis are mainly induced by an autocrine pathway and a paracrine loop of VEGF via KDR.
Zhang
Guangyu
G
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300020, China.
Zhao
Min
M
Xu
Mingtang
M
Yang
Yonghui
Y
Wang
Mengshan
M
Yang
Chunzheng
C
D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005169:Factor VIII / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000098:blood supply; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D040262:Receptors, Vascular Endothelial Growth Factor; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005169:Factor VIII; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1