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Milestone in breast cancer research

(Vienna, 26 April 2011) The Clinical Institute of Pathology is unravelling the mechanisms involved with the development of lymph node metastases in breast cancer and has demonstrated positive effects of a Chinese medicinal plant which is able to prevent the production of one of the messenger substances used by tumour cells.

“We’ve discovered how tumour cells ‘drill’ a hole in the wall of the lymphatic vessels in order to gain access to the lymph nodes in the axilla and then form metastases there," explains Institute Director Prof. Dontscho Kerjaschki. “The first step involves the cells of the primary tumour crossing the connecting channels of the lymphatic vessels into the lymph nodes. We’ve successfully deciphered how that happens, and what we can do to stop it.“

The group led by Professor Kerjaschki has found out, through many years of research, that tumour cells require a specific enzyme (lipoxygenase) to produce a bio-active metabolite of arachidonic acid (12S-HETE). This compound causes lymph vessel-forming endothelial cells to retract at the contact point with tumour cells. This is precisely the mechanism that opens up the pathway for tumour cells into the lymph nodes. In the case of breast cancer, this first occurs in the axilla, which is where the metastases then form: an opening appears in the vessel wall through which the tumour cells are able to penetrate. Based on precise microscopic observation of human tumour tissue from the biological archives of the Clinical Institute of Pathology, these findings have also been confirmed in tissue cultures and tumour models in mice.
By genetically switching off the enzyme mechanisms required to create this invasion factor, the research group has successfully prevented the penetration of the lymph vessels and therefore metastasis in the lymph nodes.

Chinese medicinal plant fights the creation of the messenger substance
The working group also discovered that a substance obtained from the roots of a Chinese medicinal plant (Scuttelaria baicalensis) is extremely effective at blocking the production of the messenger substance by tumour cells and therefore at preventing their penetration of the lymphatic vessels. This plant has already been used in traditional Asian medicine for centuries to treat various cancers.

Expertise from various working groups
Professor Kerjaschki is a strong believer in interdisciplinary collaboration: "This comprehensive work is another excellent example of how the varied expertise of different groups, when used in a coordinated and organised way, can produce results that form the starting point for new therapeutic approaches to complex diseases."
Of particular note are the contributions by the working group led by Professor Krupitza from the Clinical Institute of Pathology, which is focusing on the anti-cancer effects of natural substances, and the group led by Professor Veronica Sexl from the Institute of Pharmacology at the Medical University of Vienna (now the University of Veterinary Medicine Vienna).

The publication has appeared in the internationally renowned “Journal of Clinical Investigation”:
» Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse
Dontscho Kerjaschki, Zsuzsanna Bago-Horvath, Margaretha Rudas, Veronika Sexl, Christine Schneckenleithner, Susanne Wolbank, Gregor Bartel, Sigurd Krieger, Romana Kalt, Brigitte Hantusch, Thomas Keller, Katalin Nagy-Bojarszky, Nicole Huttary, Ingrid Raab, Karin Lackner, Katharina Krautgasser, Helga Schachner, Klaus Kaserer, Sandra Rezar, Sybille Madlener, Caroline Vonach, Agnes Davidovits, Hitonari Nosaka, Monika Hämmerle, Katharina Viola, Helmut Dolznig, Martin Schreiber, Alexander Nader, Wolfgang Mikulits, Michael Gnant, Satoshi Hirakawa, Michael Detmar, Kari Alitalo, Sebastian Nijman, Felix Offner, Thorsten J. Maier, Dieter Steinhilber and Georg Krupitza
J Clin Invest. doi:10.1172/JCI44751