Ph.D., University of Copenhagen and the Danish Cancer Society, 2000
Cancer cells are surrounded by immune cells, blood vessels, chemical signals and a support matrix – collectively, the tumor microenvironment. Most microenvironments help tumors grow and metastasize, but some can restrict tumors. My lab studies how to target the bad microenvironments and support the good ones to combat cancer.
Mikala Egeblad and colleagues study tumors and, in particular, the contributions of the microenvironment in which the cancer cells arise and live. Solid tumors are abnormally organized tissues that contain not only cancer cells, but also various stromal cell types and the extracellular matrix, and these latter components constitute the microenvironment. Communications between the different components of the tumor influence its growth, its response to therapy, and its ability to metastasize. Among the tumor-associated stromal cells, the lab’s main focus is on myeloid-derived immune cells, a diverse group of cells that can enhance angiogenesis and metastasis and suppress the cytotoxic immune response against tumors. Egeblad is interested in how different types of myeloid cells are recruited to tumors and how their behaviors—for example, their physical interactions with cancer cells and other immune cells—influence cancer progression, including metastasis. The Egeblad lab studies the importance of the myeloid cells using mouse models of breast and pancreatic cancer and real-time imaging of cells in tumors in live mice. This enables them to follow the behaviors of and the interactions between cancer and myeloid cells in tumors during progression or treatment. This technique was instrumental when the lab recently showed that cancer drug therapy can be boosted by altering components of the tumor microenvironments, specifically reducing either matrix metalloproteinases (enzymes secreted by myeloid cells) or chemokine receptors (signal receptors on myeloid cells). This year, the Egeblad lab collaborated with Scott Powers’ group to understand how normal cells surrounding a tumor promote cancer growth. They found that normal cells signal to tumors through multiple pathways, and blocking these signals together has the greatest effect on inhibiting tumor growth—offering a new strategy to fight cancer.
Nakasone, E.S., Askautrud, H.A., Kees , T., Parks, J.-H., Plaks, V., Ewald, A.J., Fein, M., Rasch, M.G., Tan, Y.X., Qiu, J., Park, J., Sinha, P., Bissell, M., Frengen, E., Werb, Z., and Egeblad, M. 2012. Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell 21: 488–503.
Engelhardt, J.J., Boldajipour, B., Beemiller, P., Pandurangi, P., Sorenson, C., Werb, Z., Egeblad, M., and Krummel, M.F. 2012. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell 21: 402–417.
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.
September 19, 2013
Live imaging shows response to cancer drugs can be boosted by altering tumor microenvironment
DoD Era of Hope Scholar Award