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Research Programs

Discipline-based Programs

Leadership

Leader: Jack Lawler, PhD

Angiogenesis, Invasion, and Metastasis

Tumor progression is a complex and multifaceted process that involves initiation, growth, invasion, and metastasis. In 1975, Dr. Judah Folkman proposed that tumors would not grow beyond the limits of diffusion without stimulating a vascular system for the delivery of nutrients. Subsequent studies have validated this hypothesis and have identified key stimulators and inhibitors of angiogenesis that function along with the tumor microenvironment to regulate tumor growth. The relative concentrations of these stimulators and inhibitors determine endothelial cell phenotype, with the change from a quiescent to angiogenic phenotype referred to as the “angiogenic switch.” The tumor vasculature also provides tumor cells with a pathway through which to enter the circulation and metastasize.

A comprehensive understanding of the many steps and processes that occur during cancer progression must include the response of the tissues in the immediate vicinity of the tumor, as well as the systemic changes that occur in the bone marrow, circulation and sites of metastasis. The tumor microenvironment is a complex tissue composed of extracellular matrix, vascular and lymphatic endothelial cells, activated fibroblasts, immune cells, pericytes, and other cell types, collectively termed the tumor stroma. Stromal cells and the components of the extracellular matrix, including its associated growth factors and the cellular proteases, regulate angiogenesis, as well as tumor cell invasion and metastasis through an interaction with integrins, proteoglycans and other cell surface receptors. Taken together, current data support the hypothesis that dynamic and reciprocal interactions between the tumor cells and the stromal cells of the tumor microenvironment determine the course of tumor progression and are central to the processes of angiogenesis, invasion and metastasis.

The working group has six principal objectives:

1. To determine the molecular and cellular processes that control tumor angiogenesis, invasion, and metastasis.

2. To promote the identification of new therapeutic targets, translational research, and clinical trials.

3. To foster the exchange of ideas among members through symposia and regularly scheduled meetings.

4. To encourage the exchange of reagents and experimental models through the development of cell and tissue repositories and databases.

5. To stimulate the development of collaborative grants for both academic and industrial sponsorship.

6. To provide mentoring and assist in career development of junior faculty.

Links:

Course in Analytical Techniques for the Quantitation of Angiogenesis and Lymphoangiogenesis
Dec 8 - 11, 2009   NIH

North American Vascular Biology Organization

Angiogenesis Gordon Conference

Tumor Microenvironment Network