The growth and spread of cancer involves not just the malignant cells themselves, but also other "host" cells in the tumor microenvironment. For example, angiogenesis provides oxygen and nutrients to the cancer cells, and also provides a mechanism by which cancer cells metastasize. Inflammatory and immune cells play important cooperating roles by generating a hospitable environment for both tumor growth and metastasis. And stromal cells such as fibroblasts are often also sources of growth factors that promote tumor growth, as well as the proteases that degrade and remodel the extracellular matrix, and thus change the adhesive properties of the cancer cells. The goals of the Tumor Microenvironment Program are to understand the molecular basis for the cell/cell and cell/matrix interactions, cell adhesions and cell migrations that take place during tumorigenesis, and to define how to limit tumorigenesis with chemical or biological inhibitors of cancer cells and the tumor microenvironment. The Tumor Microenvironment Program (TME) was formed in 2007 by merging the Cell Adhesion & Extracellular Matrix Program with the Glycobiology Program, to take advantage of and further promote the synergies already existing in the two programs. The Program consists of 16 interactive laboratories, with expertise in structural biology, carbohydrate chemistry, cryoelectron microscopy, computational analyses, signal transduction, integrin biology and animal models of tumor growth and metastasis. The research in the Program can be described in terms of three overiapplng themes: mechanisms and contributions of vascular and lymphoid components to tumor progression;the basic biology of metastasis (including the role of proteases);and the contribution of carbohydrate modifications to cancer invasion and progression. In addition, program members have an emerging interest in exploring the role of metabolism in cancer progression. In the last funding period, 3 new recruits were added to the Program, including the Program Leader, Dr. Sara Courtneidge. Members interact at a number of levels, including monthly faculty meetings, a recently established postdoc retreat, and through collaborative grants. Program funding is strong, with current total annual grant funding of $31.6MM ($18.3MM direct). Program Members currently lead or participate in 25 ROIs (14 from NCI), 6 P01s (4 from NCI), and 9 U54/U19 grants (1 from NCI). Our productivity is reflected in our 430 publications since last review, and by 81 Program publications in 2008, with 12% intra- and 13% inter-programmatic collaborations.

Public Health Relevance

The complex interactions that take place in the tumor microenvironment promote cancer cell survival, tumor growth and metastasis. It follows that investigation of these interactions and how they are controlled will deepen our understanding of tumor progression, and is also likely to provide new targets for cancer therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA030199-32
Application #
8473817
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
32
Fiscal Year
2013
Total Cost
$183,599
Indirect Cost
$100,415
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Lechtenberg, Bernhard C; Rajput, Akhil; Sanishvili, Ruslan et al. (2016) Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation. Nature 529:546-50
Zhong, Zhenyu; Umemura, Atsushi; Sanchez-Lopez, Elsa et al. (2016) NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell 164:896-910
Olson, Erika J; Lechtenberg, Bernhard C; Zhao, Chunxia et al. (2016) Modifications of a Nanomolar Cyclic Peptide Antagonist for the EphA4 Receptor To Achieve High Plasma Stability. ACS Med Chem Lett 7:841-6
Tinoco, Roberto; Carrette, Florent; Barraza, Monique L et al. (2016) PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion. Immunity 44:1190-203
Zhao, Wei; Mazar, Joseph; Lee, Bongyong et al. (2016) The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes. J Invest Dermatol 136:819-28
Singec, Ilyas; Crain, Andrew M; Hou, Junjie et al. (2016) Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling. Stem Cell Reports 7:527-42
McQuary, Philip R; Liao, Chen-Yu; Chang, Jessica T et al. (2016) C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension. Cell Rep 14:2059-67
Moscat, Jorge; Karin, Michael; Diaz-Meco, Maria T (2016) p62 in Cancer: Signaling Adaptor Beyond Autophagy. Cell 167:606-609
Miletic, Ana V; Jellusova, Julia; Cato, Matthew H et al. (2016) Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells. J Immunol 196:2195-204
Koh, Mei Yee; Gagea, Mihai; Sargis, Timothy et al. (2016) A new HIF-1α/RANTES-driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice. Hepatology 63:1576-91

Showing the most recent 10 out of 425 publications