MP70-06 MICRO- AND MACRO-FLUIDIC MODELS OF PROSTATE CANCER METASTASIS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2018MP70-06 MICRO- AND MACRO-FLUIDIC MODELS OF PROSTATE CANCER METASTASIS Takahiro Osawa, Stephen Robinson, Brendan Leung, Jinlu Dai, Shunichi Takayama, and Evan T. Keller Takahiro OsawaTakahiro Osawa More articles by this author , Stephen RobinsonStephen Robinson More articles by this author , Brendan LeungBrendan Leung More articles by this author , Jinlu DaiJinlu Dai More articles by this author , Shunichi TakayamaShunichi Takayama More articles by this author , and Evan T. KellerEvan T. Keller More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2250AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastasis is a complex cascade that involves both intravasation of tumor cells into systemic circulation and extravasation into the target metastatic site. Although visualizing tumor cell motility in vivo has been established, the underlying mechanisms of tumor cell metastasis remain largely unknown. In this study, we developed an in vitro model for recapitulating an in vivo microenvironment to observe prostate carcinoma cell metastasis. METHODS To allow for high resolution and real-time imaging of tumor intravasation, we developed a micro-metastatic model by constructing a microfluidic polydimethylsiloxane (PDMS) device to mimic a primary tumor site and a metastatic site with an interconnecting vascular-type loop in three-dimensions. We also developed a macromodel device for creating a primary tumor site and metastatic sites. The primary tumor and metastatic sites were connected with vessel-mimicking tubing which was coated with type I collagen. Cell culture media was circulated between the primary and metastatic sites using a peristaltic pump. Prostate carcinoma cells (PC3/luc) were labeled with Cell Tracker® and seeded into primary tumor site containing biomimetic collagen extracellular matrix within a microfluidic device or 6-well tissue culture plate. Bone stromal cells (HS-5) were seeded into metastatic microenvironment site. RESULTS We observed in both devices intravasation and circulation of the tumor cells using fluorescent microscope and plate reader. In addition, we found tumor cells at the metastatic site in the macromodel. CONCLUSIONS In summary, we have developed several model systems that mimic key steps of the metastatic cascade including intravasation and the accompanying presence of circulating tumor cells, followed by extravasation and the accompanying presence of disseminated tumor cells. Such systems will allow both exploration of mechanisms of metastasis and development of novel biologic assays for discovery of new therapeutics. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e936 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Takahiro Osawa More articles by this author Stephen Robinson More articles by this author Brendan Leung More articles by this author Jinlu Dai More articles by this author Shunichi Takayama More articles by this author Evan T. Keller More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...