MP47-18 LYMPH NODE STROMAL CELLS ENHANCE RENAL CELL CARCINOMA GROWTH, TRANSMIGRATION, AND METASTASIS IN AN ORTHOTOPIC XENOGRAFT MODEL

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2015MP47-18 LYMPH NODE STROMAL CELLS ENHANCE RENAL CELL CARCINOMA GROWTH, TRANSMIGRATION, AND METASTASIS IN AN ORTHOTOPIC XENOGRAFT MODEL John Nelson, Jessie Gills, Ravan Moret, Xin Zhang, Grace Maresh, Ashley Richman, M'Liss Hudson, Marc Matrana, Ryan Hedgepeth, Shams Halat, Stephen Bardot, Li Li, Christudas Morais, Glenda Gobe, and David Johnson John NelsonJohn Nelson More articles by this author , Jessie GillsJessie Gills More articles by this author , Ravan MoretRavan Moret More articles by this author , Xin ZhangXin Zhang More articles by this author , Grace MareshGrace Maresh More articles by this author , Ashley RichmanAshley Richman More articles by this author , M'Liss HudsonM'Liss Hudson More articles by this author , Marc MatranaMarc Matrana More articles by this author , Ryan HedgepethRyan Hedgepeth More articles by this author , Shams HalatShams Halat More articles by this author , Stephen BardotStephen Bardot More articles by this author , Li LiLi Li More articles by this author , Christudas MoraisChristudas Morais More articles by this author , Glenda GobeGlenda Gobe More articles by this author , and David JohnsonDavid Johnson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1538AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The incidence of renal cell carcinomas (RCC) is on the rise with an estimated 63,920 new cases in 2014. Despite increased incidental detection of lower clinically staged tumors, metastatic RCC still affects up to 25% of patients at the time of diagnosis. Lymph node (LN) involvement is a strong negative prognostic indicator. LN stromal cells have been shown to enhance tumor cell growth, tumorgenicity and chemotherapy resistance in breast and colon cancer models. However, there are currently no described RCC xenograft models that explore the role of RCC/LN interactions in RCC metastasis. Our objective is the identification of molecular signals that play key roles in human RCC tumor formation and metastasis, and the characterization their activity using a unique orthotopic patient-derived xenograft (PDX) intra-renal sub-capsular (IK) injection NOD/SCID mouse model that mimics metastatic RCC under the influence of LN stromal cells. METHODS Freshly resected human RCC specimen (KiCa-Pt58) was obtained via radical nephrectomy. Six human RCC cell lines and KiCa-Pt58 cancer cells were tagged with luciferase (firefly) to enable bioluminescent imaging (BLI). RCC cells were cultured with or without human LN stromal cells (HK) for proliferation using transmigration assays. A unique PDX IK model was used to monitor tumor growth and metastasis weekly by BLI for up to 16 weeks. H&E, immunohistochemistry (IHC) staining and RT-PCR were performed on primary tumor and mouse lung specimens. RESULTS The presence of HK cells significantly enhanced the proliferation and transmigration of RCC cells. In our PDX IK model, co-injection of HK cells enhanced RCC tumor formation (in 3 out of 6 cell lines) and spontaneous distant metastasis to lung (in 4 out of 6 cell lines). Figure 1 CONCLUSIONS Our PDX model provides a platform to study the determinant factors of tumor formation and metastasis with regard to LN stromal/RCC interaction. It can lead to the development of realistic, durable, and individualized treatments for RCC patients and establish co-clinical trials. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e558 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Nelson More articles by this author Jessie Gills More articles by this author Ravan Moret More articles by this author Xin Zhang More articles by this author Grace Maresh More articles by this author Ashley Richman More articles by this author M'Liss Hudson More articles by this author Marc Matrana More articles by this author Ryan Hedgepeth More articles by this author Shams Halat More articles by this author Stephen Bardot More articles by this author Li Li More articles by this author Christudas Morais More articles by this author Glenda Gobe More articles by this author David Johnson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...