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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Sanford-Burnham Medical Research Institute
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Gong, Xiao-Min; Ding, Yi; Yu, Jinghua et al. (2015) Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines. Biochim Biophys Acta 1848:299-306
Brun, S N; Markant, S L; Esparza, L A et al. (2015) Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma. Oncogene 34:3770-9
You, Weon-Kyoo; Yotsumoto, Fusanori; Sakimura, Kenji et al. (2014) NG2 proteoglycan promotes tumor vascularization via integrin-dependent effects on pericyte function. Angiogenesis 17:61-76
Vargas, Lina M; Leal, Nancy; Estrada, Lisbell D et al. (2014) EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-? oligomers. PLoS One 9:e92309
Volkmann, Niels; Page, Christopher; Li, Rong et al. (2014) Three-dimensional reconstructions of actin filaments capped by Arp2/3 complex. Eur J Cell Biol 93:179-83
Bailey, Ann M; Zhan, Le; Maru, Dipen et al. (2014) FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol 306:G48-58
Valencia, Tania; Kim, Ji Young; Abu-Baker, Shadi et al. (2014) Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:121-35
Northcott, Paul A; Lee, Catherine; Zichner, Thomas et al. (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428-34
Kim, H; Claps, G; Moller, A et al. (2014) Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability. Oncogene 33:2004-10
Finlay, Darren; Vamos, Mitchell; Gonzalez-Lopez, Marcos et al. (2014) Small-molecule IAP antagonists sensitize cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs. Mol Cancer Ther 13:5-15

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