The research of this project is focused on a newly discovered mechanism that operates as an important determinant of the growth of tumors. Carcinomas in general, and breast cancers in particular, are known to depend on recruited mesenchymal cells that form the tumor-associated stroma and provide vital physiologic support to the epithelial cancer cells. These mesenchymal cells derive from normal host tissue adjacent to the growing tumor as well as from progenitor cells that originate in the bone marrow. However, the mechanisms that allow the recruitment of such bone marrow progenitors and the importance of their role in overall tumor growth remain poorly understood. The research described here indicates that the slow growth of indolent tumors can be attributed in some cases, and perhaps in many, to the inability of the cancer cells to effectively recruit stromal progenitors from the marrow. This defect, in turn, can be ascribed to the fact that these indolent tumor cells are unable to release endocrine signals that perturb the bone marrow, causing it to activate and mobilize into the circulation stromal precursor cells that may subsequently be recruited by the tumor cells. Without this bone marrow-activating power, these indolent tumor cells fail to effectively recruit stromal precursors from the circulation and remain either dormant or slowly growing. In contrast, some vigorously growing tumors are endowed with the endocrine signaling ability, which we term

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA080111-13
Application #
8215972
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2011-02-01
Project End
2014-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
13
Fiscal Year
2011
Total Cost
$295,175
Indirect Cost
Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
120989983
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Rashidian, Mohammad; Ingram, Jessica R; Dougan, Michael et al. (2017) Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med 214:2243-2255
Dreijerink, Koen M A; Timmers, H T Marc; Brown, Myles (2017) Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1. Endocr Relat Cancer 24:T135-T145
Hydbring, Per; Wang, Yinan; Fassl, Anne et al. (2017) Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers. Cancer Cell 31:576-590.e8
Bierie, Brian; Pierce, Sarah E; Kroeger, Cornelia et al. (2017) Integrin-?4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells. Proc Natl Acad Sci U S A 114:E2337-E2346
Wang, Yu; Woehrstein, Johannes B; Donoghue, Noah et al. (2017) Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues. Nano Lett 17:6131-6139
Dongre, Anushka; Rashidian, Mohammad; Reinhardt, Ferenc et al. (2017) Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas. Cancer Res 77:3982-3989
Dreijerink, Koen M A; Groner, Anna C; Vos, Erica S M et al. (2017) Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer. Cell Rep 18:2359-2372
Wang, Haizhen; Nicolay, Brandon N; Chick, Joel M et al. (2017) The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. Nature 546:426-430
Hydbring, Per; Wang, Yinan; Bogorad, Roman L et al. (2017) Identification of cell cycle-targeting microRNAs through genome-wide screens. Cell Cycle 16:2241-2248
Tavera-Mendoza, Luz E; Westerling, Thomas; Libby, Eric et al. (2017) Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. Proc Natl Acad Sci U S A 114:E2186-E2194

Showing the most recent 10 out of 127 publications