Journal ArticleDOI
Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis
Mihaela Skobe,Thomas Hawighorst,David A. Jackson,Remko Prevo,Lauren Janes,Paula Velasco,Lucia Riccardi,Kari Alitalo,Kevin P. Claffey,Michael Detmar +9 more
TLDR
The occurrence and biological significance of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice are established and VEGF-C is identified as a molecular link between tumor lymphang iogenesis and metastasis.Abstract:
Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (lymphangiogenesis) and the presence of intratumoral lymphatic vessels have been controversial. Using a novel marker for lymphatic endothelium, LYVE-1, we demonstrate here the occurrence of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice. Vascular endothelial growth factor (VEGF)-C overexpression in breast cancer cells potently increased intratumoral lymphangiogenesis, resulting in significantly enhanced metastasis to regional lymph nodes and to lungs. The degree of tumor lymphangiogenesis was highly correlated with the extent of lymph node and lung metastases. These results establish the occurrence and biological significance of intratumoral lymphangiogenesis in breast cancer and identify VEGF-C as a molecular link between tumor lymphangiogenesis and metastasis.read more
Citations
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Emerging Biological Principles of Metastasis
TL;DR: The cellular and molecular mechanisms involved in metastasis are summarized, with a focus on carcinomas where the most is known, and the general principles of metastasis that have begun to emerge are highlighted.
Journal ArticleDOI
Lymphangiogenesis in development and human disease
Kari Alitalo,Kari Alitalo,Tuomas Tammela,Tuomas Tammela,Tatiana V. Petrova,Tatiana V. Petrova +5 more
TL;DR: The lymphatic vasculature forms a vessel network that drains interstitial fluid from tissues and returns it to the blood in an important role in the pathogenesis of several diseases, including cancer, lymphoedema and various inflammatory conditions.
Journal ArticleDOI
Angiogenesis in cancer.
TL;DR: There is an urgent need for a new comprehensive treatment strategy combining antiangiogenic agents with conventional cytoreductive treatments in the control of cancer.
Journal ArticleDOI
Tumors as Organs: Complex Tissues that Interface with the Entire Organism
TL;DR: Understanding the complex ways in which cancer cells interact with their surroundings, both locally in the tumor organ and systemically in the body as a whole, has implications for effective cancer prevention and therapy.
Journal ArticleDOI
Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis
TL;DR: The VEGF/VPF ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates and mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases.
References
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Journal ArticleDOI
Angiogenesis in cancer and other diseases
Peter Carmeliet,Rakesh K. Jain +1 more
TL;DR: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases and integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases, but owing to several unanswered questions, caution is needed.
Journal ArticleDOI
Vascular endothelial growth factor (VEGF) and its receptors
TL;DR: Recent developments that have widened considerably the understanding of the mechanisms that control V EGF production and VEGF signal transduction are focused on and recent studies that have shed light on the mechanisms by which VEGf regulates angiogenesis are reviewed.
Journal ArticleDOI
Genes expressed in human tumor endothelium
Brad St. Croix,Carlo Rago,Carlo Rago,Victor E. Velculescu,Giovanni Traverso,Katharine E. Romans,Elizabeth A. Montgomery,Anita Lal,Gregory J. Riggins,Christoph Lengauer,Bert Vogelstein,Bert Vogelstein,Kenneth W. Kinzler +12 more
TL;DR: It is demonstrated that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.
Journal ArticleDOI
A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.
Vladimir Joukov,Katri Pajusola,Arja Kaipainen,Dmitri Chilov,Isto Lahtinen,Eola Kukk,Olli Saksela,Nisse Kalkkinen,Kari Alitalo +8 more
TL;DR: VEGF‐C is a novel regulator of endothelia, and its effects may extend beyond the lymphatic system, where Flt4 is expressed.
Journal ArticleDOI
LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan
Suneale Banerji,Jian Ni,Shu-Xia Wang,Steven Clasper,Jeffrey Su,Raija Tammi,Margaret Jones,David A. Jackson +7 more
TL;DR: LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.