Page 437 - Read Online
P. 437

J Cancer Metastasis Treat 2016;2 Suppl 1

           carcinoma, steatotic hepatoma cells, tumor growth   in:  proteolysis/invasion/angiogenesis,  inflammation/
           signalling pathways, dual kinase inhibitors        cytokine signaling, and developmental pathways/stem
                                                              cell signaling. Remarkably, mouse-specific microarray
           References                                         analysis shows that several classes of host (mouse)
                                                              genes, which include those related to  myoepithelial
           1.   White DL, Kanwal F, El Serag HB. Association between nonalcoholic   and  myofibroblast  phenotype/cytoskeleton/motility,
               fatty liver disease and risk for hepatocellular  cancer, based on   extracellular  matrix/matrix  remodeling,  inflammation/
               systematic review. Clin Gastroenterol Hepatol 2012;10:1342-59.
           2.   Baffy G, Brunt EM, Caldwell  SH. Hepatocellular  carcinoma  in   immune functions, and development/stem cells, are
               non-alcoholic  fatty  liver  disease:  an emerging menace.  J Hepatol   significantly  upregulated  in  the  orthotopic  prostate
               2012;56:1384-91.                               tumors.  These  findings  suggest  that  the  implanted
           3.   Sun B, Karin M. Obesity, inflammation, and liver cancer. J Hepatol   human PCa cells reciprocally interact with the host
               2012;56:704-13.                                prostatic cells  (both epithelial  and  non-epithelial)
           4.   Chen K, Huang YH, Chen JL. Understanding and targeting cancer stem   to  establish  a  proinflammatory  microenvironment
               cells: therapeutic implications and challenges. Acta Pharmacologica   highly conducive to PCa metastasis. Further,  we
               Sinica 2013;34:732-40.
           5.   Yamashita T, Wang XW. Cancer stem cells in the development of liver   provide multiple pieces of  evidence that  metastatic/
               cancer. J Clin Invest 2013;123:1911-8.         metastasizing PCa cells have cancer stem cell
                                                              (CSC) properties.  This data not only  advances  our
            A17                                               understanding of the biology of PCa development and
           Metastatic prostate cancer cells are endowed       progression but also lays a foundation for developing
           with cancer stem cell properties and interact      novel therapeutics to target the tumor microenvironment
                                                              as well  as rare tumorigenic and metastasis-initiating
           with host cells to establish a proinflammatory     CSCs.
           microenvironment conducive to metastasis
                                                              Key words:
           Kiera Rycaj , Hangwen Li , Mahipal Suraneni , Xin Chen ,   Prostate cancer, tumor microenvironment, metastasis,
                     1
                                2
                                                 2
                                                          1
           Collene Jeter , Tammy Calhoun-Davis , Hseuh-Ping   cancer stem cell
                                              2
                        2
           Chao , Jianhua Hu , Dean Tang 1
                2
                           2
                                                               A18
           1 Roswell Park Cancer Institute, Buffalo, USA;
           2 MD Anderson Cancer Center, Houston, USA          EGF/EGFR pathway is sufficient to
                                                              induce aggressiveness and expression of
           Prostate cancer (PCa) is the second  leading  cancer
           in  American men with an estimated 220,800 new     pluripotency markers of patients-derived
           cases and 27,540 deaths in 2015.  Androgen         glioblastoma cells
           deprivation  therapy (ADT)  is currently the mainstay            1,2              1               2
           for advanced PCa patients; unfortunately, most     Fabien Almairac , Laurent Turchi , Denys Fontaine ,
                                                              Philippe  Paquis ,  Hervé Chneiweiss ,  Marie-Pierre
                                                                                                 4
                                                                             1,2
           treated patients  eventually develop the castration-  Junier , Fanny Burel-Vandenbos , Thierry Virolle 1
                                                                   4
                                                                                          1,3
           resistant disease (CRPC). Like most other solid
           tumors, the worst outcome for PCa patients, whether   1 University Nice-Sophia Antipolis, CNRS, INSERM, institut Biologie Valrose,
           treated or not, is development of distant metastasis.   Nice, France;
           Although many PCa cell-intrinsic molecules and end-  2 3 Neurosurgery Department, University Hospital of Nice, Nice, France;
                                                              Pathology Department, University Hospital of Nice, Nice, France;
           organ factors have been implicated in the metastatic   4 University Pierre et Marie Curie, UMCR18, Neurosciences Paris Seine,
           dissemination of PCa cells, the role of primary tumor   Paris, France
           microenvironment  and the nature of the metastatic
           PCa cells remain poorly defined. Here we attempt to   Aim: Glioblastomas are the most devastating  adult
           address the two questions by combining experimental   brain neoplasms.  Recurrences are ineluctable,  and
           PCa metastasis models in NOD/SCID mice and cDNA    presumed  to be due  to the glioma-initiating  cells
           microarray-based  expression  profiling  followed  by   (GiCs). GiCs exhibit stem-cells properties such as self-
           extensive functional studies. We first show that PCa   renewal and pluripotency, and are highly tumorigenic.
           cells  implanted orthotopically (i.e. in the prostate)   EGFR  is  a  hallmark  of  infiltrative  gliomas,  and  is
           metastasize much more extensively and widely than   overexpressed  in almost 50% of glioblastomas.  Our
           those implanted ectopically (i.e. subcutaneously or s.c).   objectives were to demonstrate that glioblastoma
           Microarray-based  gene  expression  profiling  reveals   cells are  able  to  interconvert  from  a differentiated
           that  the orthotopically  implanted human PCa cells   state to a stem-like state and conversely  depending
           upregulate  several classes of  genes that  have been   on their  environment, and to  explore the  underlying
           implicated  in metastasis and  include  those involved   biological  mechanisms, particularly the EGF/EGFR/
                           Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ November 16, 2016      427
   432   433   434   435   436   437   438   439   440   441   442