Lymphangiogenesis and cancer metastasis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-08

AUTHORS

Steven A. Stacker, Marc G. Achen, Lotta Jussila, Megan E. Baldwin, Kari Alitalo

ABSTRACT

Key Points Tumour metastasis to regional lymph nodes is a crucial step in the progression of cancer. Detection of tumour cells in the lymph nodes is an indication of the spread of the tumour, and is used clinically as a prognostic tool and a guide to therapy. However, the molecular mechanisms that control the spread of cancer to the lymph nodes were unknown until recently. The proliferation of new lymphatic vessels (lymphangiogenesis) is controlled, in part, by members of the vascular endothelial growth factor (VEGF) family — namely, VEGFC and VEGFD — and their cognate receptor on lymphatic endothelium, VEGFR3. These secreted growth factors are synthesized as propeptides that are activated by proteolysis to form high-affinity ligands that activate VEGFR3 and stimulate lymphangiogenesis. The recent identification of molecular markers to discriminate between lymphatic endothelium and blood-vessel endothelium has enabled the study of lymphatic vessel formation in experimental models and in human tumours. Experimental studies with VEGFC and VEGFD have shown that they can induce tumour lymphangiogenesis and direct metastasis to the lymphatic vessels and lymph nodes. By contrast, angiogenic factors such as VEGF act to enhance the growth of tumours by promoting a more extensive blood-vessel supply. The published patterns of expression of lymphangiogenic factors in human tumours, in general, support the hypothesis that these factors promote the lymphatic spread of human tumours. The inhibition of tumour lymphangiogenesis, using inhibitory agents that are directed to VEGFC, VEGFD or its receptor VEGFR3 (for example, monoclonal antibodies, receptor bodies or tyrosine kinase inhibitors), could be useful for anti-metastatic approaches to the treatment of human cancer. More... »

PAGES

573-583

References to SciGraph publications

  • 2001-03. Clinical significance of vascular endothelial growth factor‐C (VEGF‐C) in breast cancer in BREAST CANCER RESEARCH AND TREATMENT
  • 1994-02. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant in NATURE
  • 1997. Lymphangiogenesis: Mechanisms, significance and clinical implications in REGULATION OF ANGIOGENESIS
  • 1999-03-26. Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis in BRITISH JOURNAL OF CANCER
  • 1997-05-22. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia in ONCOGENE
  • 2001-07-03. Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer in BRITISH JOURNAL OF CANCER
  • 2001-02-01. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics in NATURE MEDICINE
  • 1996-09. How cancer spreads. in SCIENTIFIC AMERICAN
  • 1993-04. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo in NATURE
  • 2002-03. Chemokines: agents for the immunotherapy of cancer? in NATURE REVIEWS IMMUNOLOGY
  • 2001-11. Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts in BRAIN STRUCTURE AND FUNCTION
  • 2001-12. Expression of angiogenic factors and tumor progression in human neuroblastoma in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 2000-09-05. Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues in BRITISH JOURNAL OF CANCER
  • 2000-02-01. Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3): A Marker of Vascular Tumors with Presumed Lymphatic Differentiation, Including Kaposi's Sarcoma, Kaposiform and Dabska-Type Hemangioendotheliomas, and a Subset of Angiosarcomas in MODERN PATHOLOGY
  • 2001-10-30. Desmoplakin is essential in epidermal sheet formation in NATURE CELL BIOLOGY
  • 2001-02-01. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis in NATURE MEDICINE
  • 2001-02-01. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3 in NATURE MEDICINE
  • 1999-08-13. VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours in BRITISH JOURNAL OF CANCER
  • 2001-07-17. The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer in BRITISH JOURNAL OF CANCER
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    http://scigraph.springernature.com/pub.10.1038/nrc863

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