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Mikala Egeblad, Ph.D. (Associate Professor)
Mikala
Egeblad
Ph.D.
Associate Professor
Ph.D., University of Copenhagen and the Danish Cancer Society, 2000
Email
Tumor microenvironment; intravital imaging; tumor-associated myeloid cells; breast cancer
Solid tumors are abnormally organized tissues that contain cancer cells, stromal cells and extracellular matrix. Communications between the different components of the tumor influence tumor progression, for example by regulating metastasis, the immune response to tumors, or the response to therapy.
Our work addresses the challenge of separating functions and behaviors of the different stromal components of the tumor. We use mouse models of breast cancer and real-time imaging of cells in tumors in live mice. This enables us to follow the behaviors of and the interactions between cancer and stromal cells in tumors during progression or treatment.
Among the tumor-associated stromal cells, our main focus is on the myeloid-derived immune cells. These cells are very diverse and can enhance angiogenesis and metastasis, and suppress the immune response against the tumor. We are addressing how different types of myeloid cells are recruited to tumors and how their behavior in the tumor microenvironment, for example their physical interactions with cancer cells and other immune cells, influence cancer progression.
Many chemotherapeutic agents have limited or transient responses in patients. This can be due to acquired resistance of the cancer cells. However, the stromal cells and the extracellular matrix can also influence drug responses, e.g. by impairing drug delivery to the cancer cells. We are addressing how therapy affects cancer and stromal cells in different microenvironment of tumors. One of our methods is to follow the response to chemotherapy in real-time in tumors in mice undergoing chemotherapeutic treatment with imaging.
Egeblad, M., Nakasone, E., and Werb, Z. 2010. The tumor as an organ: complex tissues that interface with the entire organism. Dev. Cell 18: 884–901.
Egeblad M., Rasch, M.G., and Weaver V.M. 2010. Dynamic interplay between the collagen scaffold and tumor evolution. Curr. Opin. Cell Biol. 22: 697–706.
Levental, K.R., Yu, H., Kass, L., Lakins, J.N., Egeblad, M., Erler J.T., Fong, S.F., Csiszar, K.L., Giaccia, A., Weninger, W., Yamauchi, M., Gasser, D.L., and Weaver, V.M. 2009. Matrix cross-linking forces tumor progression by enhancing integrin signaling. Cell 139: 891–906.
Egeblad, M., Ewald, A.J., Askautrud, H.A., Truitt, M.L., Welm, B.E., Bainbridge, E., Peeters, G., Krummel, M.F., and Werb, Z. 2008. Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy. Dis. Model. Mech. 1: 155–167.
Egeblad, M., and Werb, Z. 2002. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2: 161–174.