Tumor Angiogenesis
A malignant tumor, or cancer, like any healthy tissue, requires oxygen and nutrients for its growth. To this purpose a tumor induces the formation of new blood vessels from vessels present in the surrounding healthy tissues. Once formed, these vessels not only facilitate the growth of the primary tumor, but also favor the spreading of cancer cells to distant organs (metastasis). The formation of tumor blood vessels, a process also called tumor angiogenesis is so important to the tumor that if we block it tumor growth is dramatically reduced. Drugs inhibiting tumor angiogenesis have been developed and are currently used in patients with cancer, especially kidney, colon and lung cancers. Cancers can also induce the formation of lymphatic vessels, which in turn promote the spread of cancer cells to regional lymph nodes (lymph node metastases). Along with the formation of blood and lymphatic vessels, tumors also attract immune and inflammatory cells (white blood cells). While these cells are very efficient in defending us against infection, they are not effective in protecting us against cancer. Quite the contrary, immune and inflammatory cells promote tumor growth by stimulating inflammation inside of the tumor. Inflammation acts as an amplification mechanism that stimulate many events promoting tumor growth: it favors the formation of blood vessels, stimulate tumor cell growth and induce tumor cells to migrate out of the tumor and enter vessels. In this regard, it is well known that anti-inflammatory drugs such Aspirin, have anti-cancer effects. Their use in humans for cancer prevention, however, remains problematic due to potentially serous side effects.
In projects in this module, the mechanisms underlying the formation of tumor blood and lymphatic vessels are being investigated, as well as the recruitment of inflammatory cells to tumor sites and their role in promoting local tumor growth and distant metastasis formation. The projects will be carried out through cellular, biochemical and genetic experiments using isolated cells and three dimensional tissue reconstitution models in culture, as well as mice models of angiogenesis and tumor formation.
The long-term aim of the projects is to better understand the mechanisms leading to tumor growth and metastasis formation, and to identify new molecules that may serve as therapeutic targets and against which new drugs could be developed. In the perspective of developing new therapies, clinical studies are already underway in patients in collaboration with oncologists in Switzerland and abroad (so-called translational studies).