Because the xenograft cancer stem cell assays are used by all of the projects, the animal core is central to the success of this project. This assay measures self-renewal and lineage capacity, which are the hallmarks of any stem cell, therefore, as with normal stem cells, assays for cancer stem cell activity need to be evaluated for their potential to show both self-renewal and tumor propagation. The gold standard assay that fulfills these criteria is serial transplantation in animal models, which, although imperfect, is regarded as the best functional assay for these two critical criteria. In transplantation assays, cells are xenografted into an orthotopic site of immunocompromised mice that are assayed at various time points for tumor formation. To show self-renewal, cells then must be isolated from the tumors and grafted into a second recipient animal. Issues complicating transplantation assays include potential effects of the grafting site. It is known that normal stem cells can be highly dependent on signals from the surrounding stroma for function, and it is not clear what the effect may be on separating cancer stem cells from any supporting cells during the course of the assay. Experiments using mixed populations of normal and breast tumor cells in mice have shown that combining tumor cells with normal fibroblasts increases latency and decreases tumor take, whereas combining them with carcinoma-associated fibroblasts has the opposite effect. Conversely, nontumor cells placed next to tumor stroma can become independently tumorigenic, possibly due to stroma-induced genetic or epigenetic instability. The number of cells needed to form a tumor can also be affected by the addition of irradiated feeder cells or the use of Matrigel;for feeder cells, by orders of magnitude.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA139490-05
Application #
8465144
Study Section
Special Emphasis Panel (ZCA1-SRRB-C)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$277,116
Indirect Cost
$100,448
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Krampitz, Geoffrey Wayne; George, Benson M; Willingham, Stephen B et al. (2016) Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors. Proc Natl Acad Sci U S A 113:4464-9
Weiskopf, Kipp; Schnorr, Peter J; Pang, Wendy W et al. (2016) Myeloid Cell Origins, Differentiation, and Clinical Implications. Microbiol Spectr 4:
Dalerba, Piero; Sahoo, Debashis; Paik, Soonmyung et al. (2016) CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. N Engl J Med 374:211-22
Weiskopf, Kipp; Jahchan, Nadine S; Schnorr, Peter J et al. (2016) CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer. J Clin Invest 126:2610-20
Feng, Mingye; Chen, James Y; Weissman-Tsukamoto, Rachel et al. (2015) Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. Proc Natl Acad Sci U S A 112:2145-50
Jeong, Youngtae; Swami, Srilatha; Krishnan, Aruna V et al. (2015) Inhibition of Mouse Breast Tumor-Initiating Cells by Calcitriol and Dietary Vitamin D. Mol Cancer Ther 14:1951-61
McCracken, Melissa N; Cha, Adriel C; Weissman, Irving L (2015) Molecular Pathways: Activating T Cells after Cancer Cell Phagocytosis from Blockade of CD47 ""Don't Eat Me"" Signals. Clin Cancer Res 21:3597-601
Cheah, Ming T; Chen, James Y; Sahoo, Debashis et al. (2015) CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proc Natl Acad Sci U S A 112:4725-30
Feng, Weiguo; Gentles, Andrew; Nair, Ramesh V et al. (2014) Targeting unique metabolic properties of breast tumor initiating cells. Stem Cells 32:1734-45
Wang, Jianbin; Quake, Stephen R (2014) RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection. Proc Natl Acad Sci U S A 111:13157-62

Showing the most recent 10 out of 35 publications