Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis

被引:152
作者
Fujimoto, K [1 ]
Hosotani, R [1 ]
Wada, M [1 ]
Lee, JU [1 ]
Koshiba, T [1 ]
Miyamoto, Y [1 ]
Tsuji, S [1 ]
Nakajima, S [1 ]
Doi, R [1 ]
Imamura, M [1 ]
机构
[1] Kyoto Univ, Dept Surg & Surg Basic Sci, Sakyo Ku, Kyoto 60601, Japan
关键词
vascular endothelial growth factor (VEGF); platelet-derived endothelial cell growth factor (PD-ECGF); angiogenesis; microvessel density; pancreatic cancer; RT-PCR; Western blot;
D O I
10.1016/S0959-8049(98)00069-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumour angiogenesis, as assayed by microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) have become established as important prognostic indicators for many tumour types. In this study, MVD and the expression of VEGF and PD-ECGF were examined by immunohistochemical staining of 50 pancreatic cancer tissues, and the relationships between either MVD or the expression of these two angiogenic factors and the clinicopathological features, including survival, were analysed. The expression of VEGF and PD-ECGF proteins were confirmed by Western blot analysis and VEGF mRNA isoforms were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in five pancreatic cancer cell Lines. Twenty-eight (56%) of 50 pancreatic cancers were positive for VEGF protein in cancer cells, and 16 (32%) showed strong PD-ECGF staining in cancer and infiltrating cells. VEGF(121) and VEGF(165) were identified as the predominant species produced in pancreatic cancer cells. The overexpression of VEGF and PD-ECGF protein significantly correlated with high MVD (P= 0.002, 0.044, respectively). Advanced stage of disease was significantly more frequent in patients with high MVD (P= 0.025). No significant association was found between the expression of VEGF or PD-ECGF and clinicopathological features, except for tumour histology. The expression of PD-ECGF correlated with poor survival (P= 0.011), but MVD and VEGF expression were not found to be useful for the prediction of overall survival. This study suggests that VEGF and PD-ECGF may play an important role in tumour angiogenesis, and that PD-ECGF expression seems to be useful for establishing prognoses for pancreatic cancer. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1439 / 1447
页数:9
相关论文
共 42 条
  • [1] ANGIOGENESIS IN BLADDER-CANCER - RELATIONSHIP BETWEEN MICROVESSEL DENSITY AND TUMOR PROGNOSIS
    BOCHNER, BH
    COTE, RJ
    WEIDNER, N
    GROSHEN, S
    CHEN, SC
    SKINNER, DG
    NICHOLS, PW
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1995, 87 (21) : 1603 - 1612
  • [2] BOSSI P, 1995, CANCER RES, V55, P5049
  • [3] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  • [4] TUMOR VASCULAR-PERMEABILITY FACTOR STIMULATES ENDOTHELIAL-CELL GROWTH AND ANGIOGENESIS
    CONNOLLY, DT
    HEUVELMAN, DM
    NELSON, R
    OLANDER, JV
    EPPLEY, BL
    DELFINO, JJ
    SIEGEL, NR
    LEIMGRUBER, RM
    FEDER, J
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (05) : 1470 - 1478
  • [5] THE ROLE OF ANGIOGENESIS IN THE TUMOR-GROWTH OF SYRIAN-HAMSTER PANCREATIC-CANCER CELL-LINE HPD-NR
    EGAWA, SI
    TSUTSUMI, M
    KONISHI, Y
    KOBARI, M
    MATSUNO, S
    NAGASAKI, K
    FUTAMI, H
    YAMAGUCHI, K
    [J]. GASTROENTEROLOGY, 1995, 108 (05) : 1526 - 1533
  • [6] Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia
    Enholm, B
    Paavonen, K
    Ristimaki, A
    Kumar, V
    Gunji, Y
    Klefstrom, J
    Kivinen, L
    Laiho, M
    Olofsson, B
    Joukov, V
    Eriksson, U
    Alitalo, K
    [J]. ONCOGENE, 1997, 14 (20) : 2475 - 2483
  • [7] PITUITARY FOLLICULAR CELLS SECRETE A NOVEL HEPARIN-BINDING GROWTH-FACTOR SPECIFIC FOR VASCULAR ENDOTHELIAL-CELLS
    FERRARA, N
    HENZEL, WJ
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 161 (02) : 851 - 858
  • [8] MOLECULAR AND BIOLOGICAL PROPERTIES OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR FAMILY OF PROTEINS
    FERRARA, N
    HOUCK, K
    JAKEMAN, L
    LEUNG, DW
    [J]. ENDOCRINE REVIEWS, 1992, 13 (01) : 18 - 32
  • [9] WHAT IS THE EVIDENCE THAT TUMORS ARE ANGIOGENESIS DEPENDENT
    FOLKMAN, J
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1990, 82 (01): : 4 - 6
  • [10] What is the role of thymidine phosphorylase in tumor angiogenesis?
    Folkman, J
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1996, 88 (16) : 1091 - 1092