Xenograft mouse models of lymphoid malignancies as a basis for understanding tumor microenvironment
Lymphoid malignancies are cancers of immune cells that have been transformed to grow out of control. Paradoxically, these cancer cells when removed from the patient do not grow well in the laboratory. This observation suggests that the local tumor microenvironment provides cells and factors required for cancerous growth, which has not been reproduced in the laboratory. Recently, isolated human lymphoid malignant cells have been successfully grown outside of the patient after transplant into immune deficient mice (a “xenograft”, or cross-species transplant). We propose to utilize these xenograft models to study the critical microenvironment cells and factors required for growth and survival of lymphoid malignancies.
In collaboration with the laboratories of W. Richard Burack, M.D., Ph.D., in the in the department of Pathology and Laboratory Medicine, Omar S. Aljitawi, M.B.B.S. in the department of Medicine, and Clive S. Zent, M.D. in the Wilmot Cancer Institute, we are planning to utilize several lymphoid malignancy xenograft models to define cells transplanted onto a decelllularized matrix to reproduce the growth and survival of lymphoid malignant cells in the laboratory.
Engraftment of human chronic lymphocytic leukemia cells (hCD20+, brown) in an immune deficient mouse spleen showing typical follicle-like structures (arrows, Hemotoxylin and Eosin stain, H&E).
Our long-term goal is to apply these studies toward the identification of unique cell subpopulations and factors in the local tumor microenvironment of lymphoid malignancies that will aid in the diagnosis and treatment of these cancers. Additionally, we aim to advance a laboratory model of the local tumor microenvironment that will accelerate testing of therapeutic drug candidates to promote rapid clinical benefit for patients with lymphoid malignancies.
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