What is metastasis?
Metastasis occurs when cancer cells detach from a tumor, travel to distant sites in the body and develop into tumors in these new locations. Most cancer patients die from metastases. Surgery could typically cure a patient, if not for the presence of these disseminated, and often hidden, lesions.

What is involved in metastasis?
In order to successfully metastasize, a tumor cell must be capable of completing a long series of steps. These might include invading into a blood or lymphatic vessel, surviving sheer forces in the vessel, evading immune system surveillance, lodging in a new organ, and exiting the vessel into the new tissue. Once in the new tissue, the tumor cell must survive in a significantly different micro-environment. Ultimately, it must also be capable of proliferating in this “foreign” environment — responding to positive signals and ignoring negative signals— and develop into a new lesion.

Research interests.
My primary research interests center on genes that control metastasis – including those that stop a cancer cell from spreading (like brakes on a car) and those that promote it.

Currently, we are investigating a peptide (tiny protein) that stimulates the growth of pancreatic cancer. Normal pancreatic cells do not make this peptide, but the cancer cells produce their own supply. Furthermore, the receptor that detects the presence of this little peptide (like a television antenna on the outside of the cell that relays the signal to the inside) is also abnormal in many cancer cells and may hyper-stimulate the cancer cell. Both of these elements may help cells survive and grow in distant organs as pancreatic cancer spreads.

Athymic (or “nude”) mice have genetic mutations making them immune-compromised (and hairless). Where a normal mouse would destroy human cells (like a patient rejects an organ transplant), these mice have very little immune system and human cells are accepted. Using these special mice, we can study human cancers and test whether genetic changes we make in the cancer cells change their ability to grow or spread.

Cancer cells expressing green fluorescent protein.

By inserting a gene from jellyfish into cancer cells, we can engineer the cells to glow green when blue light is shined on them. This enables us to identify and track metastasizing cancer cells. The first microscope image at the left shows single cancer cells (green dots) that have lodged in the lungs of a mouse (white bar = 250 μm). The other image captures a unique event in which cancer cells are seen growing inside a blood vessel.