• Molecular Cancer Biology Program
• Center of Excellence in Cancer Biology
• Haartman Institute
• Lymphangiogenomics

Contact Information:

Kari Alitalo
M.D., Ph.D., Academy Professor
Molecular Cancer Biology Program
Biomedicum Helsinki
Haartman Institute
PO Box 63 (Haartmaninkatu 8)
FI-00014 University of Helsinki
Finland

Tel. +358 9 191 25511
Fax. +358 9 191 25510

e-mail :
firstname.surname@helsinki.fi

Administration:
Riikka Pahkala
Suvi Kilpeläinen

Research Interests

Our laboratory has discovered several receptor tyrosine kinases, particularly in endothelial cells. Some of these receptors and their ligands play important roles in tumor angiogenesis. Among the original findings are the cloning and characterisation of fibroblast growth factor receptor-4, the C-terminal Src tyrosine kinase and the first endothelial specific receptor tyrosine kinase, Tie1, as well as the VEGF-B growth factor (in collaboration with Dr. Ulf Eriksson) and determination of VEGFR-1 and NP-1 as its receptors.

Angiogenesis and permeability of blood vessels are regulated by vascular endothelial growth factor (VEGF) via its two known receptors VEGFR-1 and VEGFR-2. We cloned additional VEGF genes and receptors and obtained new insight of the molecular mechanisms regulating lymphatic vessels. VEGF-C and VEGF-D were shown to stimulate lymphangiogenesis and their receptor VEGFR-3 has been linked to human hereditary lymphedema. VEGF-C induced the growth of peritumoral lymphatic vessels and increased lymphatic metastasis rate in transgenic and tumor-implanted mice. Furthermore, soluble VEGFR-3, which blocks embryonic lymphangiogenesis, also blocked these changes. However, VEGFR-3 is also induced in blood vessels of various types of human cancer and seems to contribute to angiogenesis in at least some tumors. Ongoing experiments will address the role of these signaling pathways in embryonic and tumor angiogenesis and the mechanisms of lymphatic metastasis. The discovered molecules should allow the regulation of angiogenesis and lymphangiogenesis as well as inhibition of tumor metastasis and tissue edema involved in many diseases.

Goals

1. To define the functions of the VEGF-B, VEGF-C, VEGF-D growth factors and the VEGFR-3 receptor and their potential uses in the treatment of human diseases.

2. To define the molecular mechanisms of lymphatic metastasis of cancer and possibilities for its inhibition.

3. Functional genomic and cell biological analysis of the lymphatic vs. blood vascular endothelium.

4. To define the signal transduction pathways and functions of the Tie-1 receptor.

5. To define the function of the arterial endothelial Bmx tyrosine kinase.

6. To explore Proxl function in intestine and colorectal cancer in collaboration with Dr Tanya Petrova.

Page updated November 28, 2011

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