(Vienna, 23 March 2018) Malignant tumour cells from a primary tumour have to pass into the bloodstream in order to form metastases in other organs. It is accepted in medical research that, in breast cancer for example, tumour cells first of all enter the vascular system and then colonise the sentinel lymph nodes closest to the primary tumour. From there they travel along the lymph channels via further secondary lymph nodes and eventually find their way into the bloodstream. In a mouse model, PhD student Markus Brown from MedUni Vienna's Department of Pathology has now discovered another highly efficient and much faster route via which tumour cells already in the sentinel lymph nodes pass through their blood vessels to "invade" the vascular system, causing pulmonary metastases. The study has recently been published in the leading journal "Science".
Lymph nodes have an important filter function within the immune system and are arranged "in series" along lymphatic vessels. As a rule, malignant tumour cells first of all migrate into lymph vessels and the associated lymph nodes, where they form metastatic colonies. The sentinel lymph node is the lymph node closest to the primary tumour.
In the clinical diagnosis of breast cancer, for example, the exact size and number of tumour colonies in the lymph nodes close to the tumour site are an important prognostic factor for the development of metastases in the lung, brain or bones, for example. However, in order to reach these organs, the tumour cells must first of all pass from the lymphatic system into the vascular system. In order to design a targeted therapeutic blockade, it is necessary to understand the precise molecular processes involved in this transition. However, up until now, the corresponding underlying principles were not available.
As part of his PhD within the working group of the former head of MedUni Vienna's Department of Pathology and professor emeritus, Dontscho Kerjaschki, and working closely with Michael Sixt's laboratory at ISTA (Institute of Science and Technology Austria) in Klosterneuburg, Markus Brown (currently working at Genentec in San Francisco) infused fluorescent marker cells from a breast tumour directly into the lymph vessels of mice and monitored how they spread into the adjoining lymph node. He observed that, within a period of 48 hours, the infused tumour cells produced the molecular signs of increased aggression, migrated out of the solid tumour and found their way into special blood vessels in the lymph node. Even after such a short time, tumour cells are already circulating in the vascular system and forming pulmonary metastases.
The initial results of this basic pathogenesis research suggest that it is likely that such an entry point for tumour cells to invade the vascular system is also present in humans. These fundamental findings could represent a starting point for the conceptual development of new targeted therapeutic measures.
“Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice.” M. Brown, F. P. Assen, A. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bago-Horvath, J. V. Stein, P. Uhrin, M. Sixt, D. Kerjaschki. SCIENCE March 23, 2018. DOI: 10.1126/science.aal3662