An in Vitro Study of Breast Cancer Invasion into the Lymphatics
Final rept. 25 Jul 2005-24 Jul 2006
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (SWITZERLAND)
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Lymphatic metastasis is a major prognostic factor for breast cancer patients. Despite its importance, the mechanisms underlying lymphatic metastasis are poorly understood and the question of how cancer cells access the lymphatics i.e. whether they primarily induce lymphangiogenesis sprouting of new lymphatic vessels or invade preexisting lymphatics is debated in the literature. We challenge the notion of tumor lymphangiogenesis as the major mechanism for tumor entry into the lymphatics and suggest that the biophysical and biochemical factors induced or produced by the tumor, including VEGF-C, act to promote tumor cell migration towards lymphatics, not vice-versa. In real mammary carcinomas as opposed to subcutaneously xenografted, blood vessels are leaky, interstitial fluid pressure is high, and fluid exudes from the tissue into the surrounding stroma and eventually into the lymphatics. This biophysical environment promotes the transport of any tumor-secreted factors, including VEGF-C, from the tumor towards the lymphatics. In light of these factors, we hypothesized that tumor-secreted factors can be delivered to the lymphatics by natural biophysical forces, where it stimulates the production of tumor cytokines by the activated lymphatics, in turn promoting tumor cell invasion into surrounding lymphatics. In this one-year project, we proposed to first develop a novel tissue engineered tumor extracellular matrix ECM-lymphatic environment and then use it to answer questions relating to this novel hypothesis.
- Anatomy and Physiology
- Medicine and Medical Research