Growth factors / receptors

Relevance of various growth factors and receptors on tumor growth and tumor angiogenesis

The interplay between growth factors, receptors and binding proteins influencing ligand-receptor interactions, is of great importance in biological systems. Beyond the characterization of proteins this requires functional studies through selective interference in cellular processes. In tumors, this includes tumor cell proliferation, apoptosis and the formation of new blood vessels (angiogenesis).

One major goal of our research is to study the biological relevance of different growth factors and receptors on tumor growth and angiogenesis. 

Only the knowledge of the underlying mechanisms may allow the selective interference in these processes leading to causal therapeutic approaches.

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Abnormal expression of growth factors and receptors in cancer
(from: Paul and Mukhopadhyay, Int. J. Med. Sci., 2004)


Pleiotrophin (PTN) and the pleiotrophin receptor (PTN-R/ALK

The growth factor pleiotrophin (PTN) stimulates cell proliferation and angiogenesis and is highly expressed during embryogenesis as well as in several tumors. High PTN levels can also be detected in blood serum of tumor patients and often correlate with tumor size.

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Increased PTN serum levels in testicular carcinoma patients
(Aigner et al., Annals Oncol., 2003)

Additionally, using phage display we identified the PTN-receptor PTN-R/ ALK and showed its relevance in the growth of tumors of the brain and of the breast.

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Identification of ALK as PTN receptor (left) and overexpression of ALK in glioblastoma (right)
(Stoica et al., J. Biol. Chem., 2001)


This project aims at the further functional analysis of PTN and ALK in tumors and the elucidation of relevant biochemical pathways, as a basis for therapeutic intervention

The receptors HER-2 (c-erbB2/neu) and HER-1

HER-2 plays an important role during embryogenesis and oncogenesis. Overexpression of HER-2 is found in several human carcinomas and often correlates with a more aggressive tumor growth, a worse prognosis and a higher resistance towards chemo- and radiation therapy. Therefore, HER-2 is considered a negative prognostic factor of the disease and a target molecule in (gene) therapy.

It is also known from the literature that in the presence of a HER-1 ligand the HER-2 receptor hetero-dimerizes with HER-1 (EGFR) forming a particularly active heterodimer.

              project6

HER receptor signaling
(Zugmaier et al., Med. Welt, 2003 )

In cell culture and in vivo, we analyse the molecular effects of the single or double targeting of members of the HER family in tumors.