Neurovascular link in neuroendocrine tumors

Head of the Group

Christian Fischer

Contact


Gastrointestinal tumors exhibit distinct patterns of metastatic disease progression. Work in our group applies the paradigm of the neurovascular link to understand how tumor cells exploit the shared evolutionary origin of axon-/vessel guidance factors in specialized interactions with nerves and vessels in the tumor environment.

Pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine tumors (NETs) each occupy extreme ends within the spectrum of gastrointestinal malignancies. They both exhibit uncommon modes of metastatic progress, which require highly specialized interfaces with the host stroma. At this interface, pancreatic cancer cells contact nerves and use them as conduits for dissemination in a process called neural invasion. NET cells preferentially metastasize to the liver, and engage in extensive contact with a well-differentiated vasculature.

The neurovascular link offers a unique concept to recognize common themes and specialized features in these different ways of metastatic tumor progression. Briefly, nerves and vessels exhibit comparable structural patterning and share similar ligand-receptor cues to navigate to their target. So called axon guidance factors have originally been characterized in neurogenesis to function as molecular cues, which control growth, navigation and positioning of neurons in the developing brain. These ancient axon guidance signals from the evolutionary older nervous system were co-opted for navigational control by the emerging younger blood vessels. In turn, the vascular endothelial growth factor (VEGF) was originally discovered as the key angiogenic growth factor for angiogenesis, but subsequent evidence indicated that avascular species already express VEGF orthologs to regulate neural development and homeostasis.

We develop model systems to study the disease specific interactions of tumor cells with stromal cells in PDAC and NETs, and apply the paradigm of the neurovascular link to explain, how the shared evolutionary origin of nerves and vessels is exploited by these malignancies in their specialized interactions with the tumor microenvironment.