Abstract

In this project, we propose to address the functional contribution of hypoxic microenvironment (TME) to the progression of prostate cancer and emergence of metastatic bone disease. This project use the mouse models generated in the Project 1 to study the influence of hypoxia, EMT and myofibroblasts metabolism and validate these finding in human prostate cancer tissue. Such studies will be performed in collaboration Scadden Laboratory (Project 3), which will determine the cellular components of the bone that likely cooperate with bone metastasis. We also propose to evaluate in detail the acquisifion of the ability of cancer cell to mimic mesenchymal cell types and undergo a program of epithelial to mesenchymal transition (EMT), in hopes of gathering information to identify new therapeutic targets against metastatic prostate cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163191-02
Application #
8555537
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (O1))
Project Start
2011-09-26
Project End
2012-08-02
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$287,562
Indirect Cost
$95,082

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Chattopadhyay, Shrikanta; Stewart, Alison L; Mukherjee, Siddhartha et al. (2015) Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors. Cell Rep :
Keskin, Doruk; Kim, Jiha; Cooke, Vesselina G et al. (2015) Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2. Cell Rep 10:1066-81
Krause, Daniela S; Scadden, David T (2015) A hostel for the hostile: the bone marrow niche in hematologic neoplasms. Haematologica 100:1376-87
Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid et al. (2015) Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis. J Proteome Res 14:5252-62
Zheng, Xiaofeng; Carstens, Julienne L; Kim, Jiha et al. (2015) Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 527:525-530
Zeisberg, Michael; Tampe, Björn; LeBleu, Valerie et al. (2014) Thrombospondin-1 deficiency causes a shift from fibroproliferative to inflammatory kidney disease and delays onset of renal failure. Am J Pathol 184:2687-98
Özdemir, Berna C; Pentcheva-Hoang, Tsvetelina; Carstens, Julienne L et al. (2014) Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25:719-34
Scadden, David T (2014) Nice neighborhood: emerging concepts of the stem cell niche. Cell 157:41-50
Melo, Sonia A; Sugimoto, Hikaru; O'Connell, Joyce T et al. (2014) Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26:707-21
Charytan, David M; Padera, Robert; Helfand, Alexander M et al. (2014) Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease. Int J Cardiol 176:99-109

Showing the most recent 10 out of 17 publications