Morten Grønbech Rasch returns to Finsen Laboratory after six months at Cold Spring Harbor Laboratory in USA
The stay was a part of Morten’s Ph.D.
As part of my second year as a Ph.D. student at the Finsen Laboratory, I recently spend six months in Ass. Prof. Mikala Egeblads group at Cold Spring Harbor Laboratory (CSHL). The Purpose of this stay was mainly to receive training in spinning-disc confocal microscopy of live mice, a technique Dr. Egeblad and colleagues has pioneered. With this technique it is possible to visualize the cell response to various anti-cancer treatments in live animals to confirm actions. Observations of this type are fundamental for the understanding of the molecular mechanisms that determine whether a particular treatment works or not. In addition, Dr. Egeblad has a very strong background in cancer biology and particularly in the field of extracellular matrix remodeling, which is an essential part of my own Ph.D. project. Therefore, I also expected to increase my general knowledge in the field through discussions with Dr. Egeblad.
Malignant tumors are surrounded by an extracellular matrix, which serves as a physical barrier against invasive growth. Cancer invasion and tissue remodeling is an essential event during cancer progression and the cellular and biochemical mechanisms responsible for the breakdown of matrix in tumor growth and metastasis are therefore promising targets for therapeutic intervention. Several proteases are involved in this process and among these are matrix metalloprotease-9 (MMP-9), which has been shown to be important for disease progression in genetically induced mouse models of skin -, cervix - and pancreas cancer.
The main project I worked on during my time at CSHL was characterization of the role of MMP-9 in two different genetically induced murine breast cancer models. Initial data showed that MMP-9 played different roles in the two different types of breast cancer, but the specific mechanism for this was not yet clarified. In order to further investigate this I characterized and quantified the infiltration of myeloid cells using immunohistochemistry and immunofluorescence. This was coupled with an analysis of the chemokine environment in tumors from the two different models. From these data we were able to draw conclusions, which can explain the different roles of MMP-9 we detect in the two breast cancer models.
My Ph.D. project at the Finsen Laboratory involves generation and characterization of monoclonal antibodies directed against murine matrix metalloprotease-9 (MMP-9). I brought a panel of these mAbs to Dr. Egeblads lab in order to investigate their suitability for in vivo imaging purposes. We did a range of imaging sessions in order to optimize the use of the MMP-9 mAbs and collected a lot of interesting data on the migrational behavior of MMP-9 expressing cells in breast tumors.
I have incorporated the majority of the data I generated at Dr. Egeblads laboratory in my own Ph.D. project and we have currently several exciting publications in the pipeline.
