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 #
3P30CA030199-31S1
Application #
8473792
Study Section
Subcommittee G - Education (NCI)
Project Start
1997-05-01
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
31
Fiscal Year
2012
Total Cost
$7,940
Indirect Cost
$3,783
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Barile, Elisa; Marconi, Guya D; De, Surya K et al. (2017) hBfl-1/hNOXA Interaction Studies Provide New Insights on the Role of Bfl-1 in Cancer Cell Resistance and for the Design of Novel Anticancer Agents. ACS Chem Biol 12:444-455
Attali, Ilan; Tobelaim, William Sam; Persaud, Avinash et al. (2017) Ubiquitylation-dependent oligomerization regulates activity of Nedd4 ligases. EMBO J 36:425-440
Linares, Juan F; Cordes, Thekla; Duran, Angeles et al. (2017) ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma. Cell Metab 26:817-829.e6
Todoric, Jelena; Antonucci, Laura; Di Caro, Giuseppe et al. (2017) Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas. Cancer Cell 32:824-839.e8
Scortegagna, Marzia; Berthon, Annabel; Settas, Nikolaos et al. (2017) The E3 ubiquitin ligase Siah1 regulates adrenal gland organization and aldosterone secretion. JCI Insight 2:
Jellusova, Julia; Cato, Matthew H; Apgar, John R et al. (2017) Gsk3 is a metabolic checkpoint regulator in B cells. Nat Immunol 18:303-312
Avellaneda Matteo, Diego; Grunseth, Adam J; Gonzalez, Eric R et al. (2017) Molecular mechanisms of isocitrate dehydrogenase 1 (IDH1) mutations identified in tumors: The role of size and hydrophobicity at residue 132 on catalytic efficiency. J Biol Chem 292:7971-7983
Lee, Bongyong; Sahoo, Anupama; Marchica, John et al. (2017) The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre-mRNA molecules. Sci Adv 3:e1602505
McKeithan, Wesley L; Savchenko, Alex; Yu, Michael S et al. (2017) An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes. Front Physiol 8:766
Toome, Kadri; Willmore, Anne-Mari A; Paiste, Päärn et al. (2017) Ratiometric in vivo auditioning of targeted silver nanoparticles. Nanoscale 9:10094-10100

Showing the most recent 10 out of 483 publications