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. and Askautrud, H. A. and Kees, T. and Park, J. H. and Plaks, V. and Ewald, A. J. and Fein, M. and Rasch, M. G. and Tan, Y. X. and Qiu, J. and Park, J. and Sinha, P. and Bissell, M. J. and Frengen, E. and Werb, Z. and Egeblad, M. (2012) Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance. Cancer Cell 21(4) pp. 488-503.
Engelhardt, J. J. and Boldajipour, B. and Beemiller, P. and Pandurangi, P. and Sorensen, C. and Werb, Z. and 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(3) pp. 402-417.
Egeblad, M. and Rasch, M. G. and Weaver, V. M. (2010) Dynamic interplay between the collagen scaffold and tumor evolution. Current Opinion in Cell Biology 22(5) pp. 697-706.
Egeblad, M. and Nakasone, E. S. and Werb, Z. (2010) Tumors as Organs: Complex Tissues that Interface with the Entire Organism. Developmental Cell 18(6) pp. 884-901.
Levental, K. R. and Yu, H. and Kass, L. and Lakins, J. N. and Egeblad, M. and Erler, J. T. and Fong, S. F. T. and Csiszar, K. and Giaccia, A. and Weninger, W. and Yamauchi, M. and Gasser, D. L. and Weaver, V. M. (2009) Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling. Cell 139(5) pp. 891-906.Additional materials of the author at
CSHL Institutional Repository
September 19, 2013
Live imaging shows response to cancer drugs can be boosted by altering tumor microenvironment
DoD Era of Hope Scholar Award