Research Associate and Lab Manager, Dr. John Lewis Laboratory, Department of Oncology, University of Alberta
Prostate cancer, like many other tumors, requires the formation of new blood vessels through de novo angiogenesis. This is a fundamental process in the growth of the tumor mass as well as nutrient and oxygen delivery to, and toxin removal from, the tumor. Without proper vascularization the tumor starts to die and decreases in size. Thus, the tumor ensures its well-being, sending messages (angiogenic factor(s)) to its surrounding environment, which allows vascularization to form from the existing host vasculature network.
While successful drugs to inhibit angiogenesis in tumors have been identified, one of the key areas of angiogenesis research is the choice of appropriate assays to evaluate the efficacy of potential new drugs, and to identify potential targets within the angiogenic process. We have developed an efficient and cost-effective, in vivo angiogenesis assay using an ex ovo chicken chorioallantoic model. Our chorioallantoic membrane (CAM) assay allows simultaneous, quantitative evaluation of many compounds, in a short period of time. In brief, human tumor cells or exogenous compounds (potentially promoting or inhibiting angiogenesis) are mixed into a collagen onplant to provide the pro- or anti-angiogenic signal. This onplant is placed onto the CAM for 3 days and new blood vessels are visualized and scored with a basic stereomicroscope. Thus, the relative “angiogenic potential” of different cell lines or drugs can be evaluated.
Adam Kinnaird, Roxane Paulin, Desmond B. Pink, Evangelos D. Michelakis, Peter Dromparis, Sotirios Zervopoulos, Katia Carmine-Simmen, Bruno Saleme, Trevor Stenson, Ronald Moore, Vikram Gurtu, Gopinath, John D Lewis, Kristalee Watson. Metabolic Modulation of Clear-cell Renal Cell Carcinoma with Dichloroacetate, an Inhibitor of Pyruvate Dehydrogenase Kinase. Eur Urol. 2015 Sep 30;
Haile Y, Carmine-Simmen K, Olechowski C, Kerr B, Bleackley RC, Giuliani F. Granzyme B-inhibitor serpina3n induces neuroprotection in vitro and in vivo. J Neuroinflammation. 2015 Sep 4;12(1):157.
Farhan MA, Carmine-Simmen K, Lewis JD, Moore RB, Murray AG. Endothelial Cell mTOR Complex-2 Regulates Sprouting Angiogenesis. PLoS One. 2015 Aug 21;10(8)
Marcet-Palacios M, Ewen C, Pittman E, Duggan B, Carmine-Simmen K, Fahlman RP, Bleackley RC. Design and characterization of a novel human Granzyme B inhibitor. Protein Eng Des Sel. 2015 Jan;28(1):9-17
Leong HS, Robertson AE, Stoletov K, Leith SJ, Chin CA, Chien AE, Hague MN, Ablack A, Carmine-Simmen K, McPherson VA, Postenka CO, Turley EA, Courtneidge SA, Chambers AF, Lewis JD. Invadopodia are required for cancer cell extravasation and are a therapeutic target for metastasis. Cell Rep. 2014 Sep 11;8(5):1558-70.
Wentzell JS, Bolkan BJ, Carmine-Simmen K, Swanson TL, Musashe DT, Kretzschmar D. Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration. Neurobiol Dis. 2012 Apr;46(1):78-87
Haile Y, Simmen KC, Pasichnyk D, Touret N, Simmen T, Lu JQ, Bleackley RC, Giuliani F. Granule-Derived Granzyme B Mediates the Vulnearability of Human Neurons to T Cell-Induced Neurotoxicity. J. Immunol. 2011 Nov 1; 187(9):4861-72. Epub 2011 Sep 30.
Ang LS, Boivin WA, Williams SJ, Zhao H, Abraham T, Carmine-Simmen K, McManus BM, Bleackley RC, Granville DJ. Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm. Cell Death Dis. 2011 Sep 8; 2:209-2018.
Carmine-Simmen K, Proctor T, Tschape J, Poeck B, Triphan T, Strauss R, Kretzschamar D. Neurotoxic effects induced by the Drosophila amyloid-beta peptide suggest a conserved toxic function. Neurobiol Dis. 2009 Feb;33(2):274-81. Epub 2008 Nov 8.
Myhill N, Lynes EM, Nanji JA, Blagoveshchenskaya AD, Fei H, Carmine Simmen K, Cooper TJ, Thomas G, Simmen T. The subcellular distribution of calnexin is mediated by PACS-2. Mol Biol Cell. 2008 Jul; 19 (7):2777-88. Epub 2008 Apr 16.
Sipione S, Simmen KC, Lord SJ (co-first author), Motyka B, Ewen C, Shostak I, Rayat GR, Dufour JM, Korbutt GS, Rajotte RV, & Bleackley RC, Identification of a novel human granzyme B inhibitor secreted by cultured sertoli cells. J Immunol, 2006. 177(8): p. 5051-8.
Kottgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, Huber TB, Schermer B, Kramer-Zucker A, Hopker K, Simmen KC, Tschucke CC, Sandford R, Kim E, Thomas G, & Walz G. (2005). Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. Embo J, 24, 705-716.
Ferrari S, Simmen KC (co-first author), Dusserre Y, Muller K, Fourel G, Gilson E, & Mermod N. Chromatin domain boundaries delimited by a histone-binding protein in yeast. J Biol Chem, 2004 279, 55520-55530.
Spataro V, Simmen K. & Realini CA. The essential 26S proteasome subunit Rpn11 confers multidrug resistance to mammalian cells. Anticancer Res, 2002 22, 3905-3909.
Fourel G, Boscheron C, Revardel E, Lebrun E, Hu YF, Simmen KC, Muller K, Li R, Mermod N, & Gilson, E. An activation-independent role of transcription factors in insulator function. EMBO Rep, 2001 2, 124-132.