Accumulating evidence has shown that the tumor microenvironment is critically important for the initiation and progression of cancer. The tumor microenvironment consists of several components including tumor cells, myofibroblasts, stellate cells, peritumor nerve cells, endothelial cells, immune cells and endocrine cells, as well as extracellular components such as the extracellular matrix. While it is recognized that these components are mediators of tumorigenesis, the complex interplay of these components is poorly understood. Research efforts to investigate the mechanisms of tumor microenvironment interactions in the primary tumor site and organs that are common sites of metastatic lesions are critically needed in order to identify potential targets for improved cancer treatment, as well as risk management and prevention. Hence, we believe that there is a clear need for new programs to train individuals at the graduate as well as the postgraduate levels to understand and efficiently investigate the complex processes that contribute to the conversion of normal stromal cells to an active tumor microenvironment that leads to tumor progression and metastasis. This proposal requests funding to support is 8 trainees (2 predoctoral, 6 postdoctoral) each year for 5 years The program objective is to provide integrated training to individuals who will conduct critically needed research investigating the molecular and cellular anomalies of tumor microenvironment components that result in tumor initiation, progression, metastasis, and relapse. The program is based on the idea that major progress, of clinical relevance, in the area of stromal and epithelial dysfunction of cancer formation will be enhanced by a concerted effort of investigators who have had substantial mentoring and experience in the fields of cell biology, vascular cell biology, extracellular matrix biology, cancer genetics, immunology, and clinical cancer research. The Tumor Microenvironment/Angiogenesis (TMA) Training Program involves 25 full faculty members, all of whom have extramurally supported programs and expertise in TMA-related areas. Dr. Mukhopadhyay will serve as director of the program. He is an experienced mentor and training program leader. He will be assisted by Dr. Mark McNiven, who is known world-wide for his expertise in cell biology and he has an outstanding training record.

Public Health Relevance

Despite the tremendous advancements in the diagnosis and treatment of cancer, we are far from achieving our optimal goal to """"""""eradicate cancer."""""""" This training program will program will provide the next generation of cancer researchers with an integrated set of skills needed to understand the complex interactions of tumor cells and the cells surrounding them. This knowledge will be used to improve cancer prevention and treatment methods.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Institutional National Research Service Award (T32)
Project #
5T32CA148073-02
Application #
8069951
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lim, Susan E
Project Start
2010-06-01
Project End
2015-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
2
Fiscal Year
2011
Total Cost
$232,337
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Javeed, Naureen; Mukhopadhyay, Debabrata (2017) Exosomes and their role in the micro-/macro-environment: a comprehensive review. J Biomed Res 31:386-394
Sagar, Gunisha; Sah, Raghuwansh P; Javeed, Naureen et al. (2016) Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue. Gut 65:1165-74
Somasundaram, Veena; Hemalatha, Sreelatha K; Pal, Krishnendu et al. (2016) Selective mode of action of plumbagin through BRCA1 deficient breast cancer stem cells. BMC Cancer 16:336
Hoeppner, Luke H; Sinha, Sutapa; Wang, Ying et al. (2015) RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells. J Cell Sci 128:3556-68
Leonard, Phoebe H; Grzenda, Adrienne; Mathison, Angela et al. (2015) The Aurora A-HP1? pathway regulates gene expression and mitosis in cells from the sperm lineage. BMC Dev Biol 15:23
Hoeppner, Luke H; Wang, Ying; Sharma, Anil et al. (2015) Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells. Mol Oncol 9:270-81
Deng, Zhi-Hui; Gomez, Timothy S; Osborne, Douglas G et al. (2015) Nuclear FAM21 participates in NF-?B-dependent gene regulation in pancreatic cancer cells. J Cell Sci 128:373-84
Phillips-Krawczak, Christine A; Singla, Amika; Starokadomskyy, Petro et al. (2015) COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. Mol Biol Cell 26:91-103
Javeed, Naureen; Sagar, Gunisha; Dutta, Shamit K et al. (2015) Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic ?-cell Dysfunction. Clin Cancer Res 21:1722-33
Wang, Ying; Cao, Ying; Yamada, Satsuki et al. (2015) Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-? Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1? and Mitochondrial Homeostasis. Arterioscler Thromb Vasc Biol 35:1401-12

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