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From the Departments of Oncology*
Otolaryngology,§
Helsinki University Central
Hospital, and the Molecular/Cancer Biology
Laboratory
and Department of
Pathology,
Haartman Institute, University of
Helsinki, Helsinki, Finland; and the Ludwig Institute for Cancer
Research,¶
Stockholm, Sweden
The growth of solid tumors is dependent on angiogenesis, the formation of new blood vessels. Vascular endothelial growth factor (VEGF) is a secreted endothelial-cell-specific mitogen. We have recently characterized two novel endothelial growth factors with structural homology to VEGF and named them VEGF-B and VEGF-C. To further define the roles of VEGF-B and VEGF-C, we have studied their expression in a variety of human tumors, both malignant and benign. VEGF-B mRNA was detected in most of the tumor samples studied, and the mRNA and the protein product were localized to tumor cells. Endothelial cells of tumor vessels were also immunoreactive for VEGF-B, probably representing the binding sites of the VEGF-B polypeptide secreted by adjacent tumor cells. VEGF-C mRNA was detected in approximately one-half of the cancers analyzed. Via in situ hybridization, VEGF-C mRNA was also localized to tumor cells. All lymphomas studied contained low levels of VEGF-C mRNA, possibly reflecting the cell-specific pattern of expression of the VEGF-C gene in the corresponding normal cells. The expression of VEGF-C is associated with the development of lymphatic vessels, and VEGF-C could be an important factor regulating the mutual paracrine relationships between tumor cells and lymphatic endothelial cells. Furthermore, VEGF-C and VEGF-B can, similarly to VEGF, be involved in tumor angiogenesis.
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T. Karpanen, M. Egeblad, M. J. Karkkainen, H. Kubo, S. Ylä-Herttuala, M. Jäättelä, and K. Alitalo Vascular Endothelial Growth Factor C Promotes Tumor Lymphangiogenesis and Intralymphatic Tumor Growth Cancer Res., March 1, 2001; 61(5): 1786 - 1790. [Abstract] [Full Text]
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S. Hiratsuka, Y. Maru, A. Okada, M. Seiki, T. Noda, and M. Shibuya Involvement of Flt-1 Tyrosine Kinase (Vascular Endothelial Growth Factor Receptor-1) in Pathological Angiogenesis Cancer Res., February 1, 2001; 61(3): 1207 - 1213. [Abstract] [Full Text]
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H.-Q. MIAO, P. LEE, H. LIN, S. SOKER, and M. KLAGSBRUN Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression FASEB J, December 1, 2000; 14(15): 2532 - 2539. [Abstract] [Full Text]
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P. Salven, A. Orpana, L. Teerenhovi, and H. Joensuu Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients Blood, December 1, 2000; 96(12): 3712 - 3718. [Abstract] [Full Text] [PDF]
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S. P. Gunningham, M. J. Currie, C. Han, B. A. Robinson, P. A. E. Scott, A. L. Harris, and S. B. Fox The Short Form of the Alternatively Spliced flt-4 but not Its Ligand Vascular Endothelial Growth Factor C Is Related to Lymph Node Metastasis in Human Breast Cancers Clin. Cancer Res., November 1, 2000; 6(11): 4278 - 4286. [Abstract] [Full Text] [PDF]
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T. A. PARTANEN, J. AROLA, A. SAARISTO, L. JUSSILA, A. ORA, M. MIETTINEN, S. A. STACKER, M. G. ACHEN, and K. ALITALO VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues FASEB J, October 1, 2000; 14(13): 2087 - 2096. [Abstract] [Full Text]
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A. J. Leu, D. A. Berk, A. Lymboussaki, K. Alitalo, and R. K. Jain Absence of Functional Lymphatics within a Murine Sarcoma: A Molecular and Functional Evaluation Cancer Res., August 1, 2000; 60(16): 4324 - 4327. [Abstract] [Full Text]
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T. Niki, S. Iba, M. Tokunou, T. Yamada, Y. Matsuno, and S. Hirohashi Expression of Vascular Endothelial Growth Factors A, B, C, and D and Their Relationships to Lymph Node Status in Lung Adenocarcinoma Clin. Cancer Res., June 1, 2000; 6(6): 2431 - 2439. [Abstract] [Full Text]
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A. Eggert, N. Ikegaki, J. Kwiatkowski, H. Zhao, G. M. Brodeur, and B. P. Himelstein High-Level Expression of Angiogenic Factors Is Associated with Advanced Tumor Stage in Human Neuroblastomas Clin. Cancer Res., May 1, 2000; 6(5): 1900 - 1908. [Abstract] [Full Text]
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 J. C. Gollmer, A. Ladoux, J. Gioanni, P. Paquis, A. Dubreuil, M. Chatel, and C. Frelin Expression of vascular endothelial growth factor-b in human astrocytoma Neuro-oncol, April 1, 2000; 2(2): 80 - 86. [Abstract] [PDF]
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 G. Gasparini Prognostic Value of Vascular Endothelial Growth Factor in Breast Cancer Oncologist, April 1, 2000; 5(90001): 37 - 44. [Abstract] [Full Text]
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H. Yonekura, S. Sakurai, X. Liu, H. Migita, H. Wang, S.-i. Yamagishi, M. Nomura, Md. J. Abedin, H. Unoki, Y. Yamamoto, et al. Placenta Growth Factor and Vascular Endothelial Growth Factor B and C Expression in Microvascular Endothelial Cells and Pericytes. IMPLICATION IN AUTOCRINE AND PARACRINE REGULATION OF ANGIOGENESIS J. Biol. Chem., December 3, 1999; 274(49): 35172 - 35178. [Abstract] [Full Text] [PDF]
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P. Salven, L. Teerenhovi, and H. Joensuu A High Pretreatment Serum Basic Fibroblast Growth Factor Concentration Is an Independent Predictor of Poor Prognosis in Non-Hodgkin's Lymphoma Blood, November 15, 1999; 94(10): 3334 - 3339. [Abstract] [Full Text] [PDF]
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J. Tomlinson, S. H. Barsky, S. Nelson, S. Singer, B. Pezeshki, M. C. Lee, F. Eilber, and M. Nguyen Different Patterns of Angiogenesis in Sarcomas and Carcinomas Clin. Cancer Res., November 1, 1999; 5(11): 3516 - 3522. [Abstract] [Full Text] [PDF]
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G. Siemeister, M. Schirner, K. Weindel, P. Reusch, A. Menrad, D. Marme, and G. Martiny-Baron Two Independent Mechanisms Essential for Tumor Angiogenesis: Inhibition of Human Melanoma Xenograft Growth by Interfering with either the Vascular Endothelial Growth Factor Receptor Pathway or the Tie-2 Pathway Cancer Res., July 1, 1999; 59(13): 3185 - 3191. [Abstract] [Full Text] [PDF]
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R. Valtola, P. Salven, P. Heikkila, J. Taipale, H. Joensuu, M. Rehn, T. Pihlajaniemi, H. Weich, R. deWaal, and K. Alitalo VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer Am. J. Pathol., May 1, 1999; 154(5): 1381 - 1390. [Abstract] [Full Text] [PDF]
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R. F. Nicosia What Is the Role of Vascular Endothelial Growth Factor-Related Molecules in Tumor Angiogenesis? Am. J. Pathol., July 1, 1998; 153(1): 11 - 16. [Full Text] [PDF]
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V. Nurcombe, C. E. Smart, H. Chipperfield, S. M. Cool, B. Boilly, and H. Hondermarck The Proliferative and Migratory Activities of Breast Cancer Cells Can Be Differentially Regulated by Heparan Sulfates J. Biol. Chem., September 22, 2000; 275(39): 30009 - 30018. [Abstract] [Full Text] [PDF]
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