SPARC-independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic Cancer xenografts

Academic Article

Abstract

  • © 2016 American Association for Cancer Research. The study goal was to examine the relationship between nabpaclitaxel delivery and SPARC (secreted protein acidic and rich in cysteine) expression in pancreatic tumor xenografts and to determine the antistromal effect of nab-paclitaxel, which may affect tumor vascular perfusion. SPARC-positive and-negative mice bearing Panc02 tumor xenografts (n=5-6/group) were injected with IRDye800CW(IR800)-labeled nab-paclitaxel. After 24 hours, tumorswerecollectedandstainedwithDL650-labeledanti-SPARC antibody, and the correlation between nab-paclitaxel and SPARC distributions was examined. Eight groups of mice bearing either Panc039 or Panc198 patient-derived xenografts (PDX; 4 groups/model, 5 animals/group) were untreated (served as control) or treated with gemcitabine (100 mg/kg body weight, i.p., twice per week), nab-paclitaxel (30mg/kgbodyweight, i.v., for5consecutive days), and these agents in combination, respectively, for 3 weeks, and tumor volume and perfusion changes were assessed using T2-weightedMRIanddynamiccontrast-enhanced(DCE)MRI, respectively. All tumors were collected and stained with Masson's Trichrome Stain, followed by a blinded comparative analysis of tumor stroma density. IR800-nab-paclitaxel was mainly distributed in tumor stromal tissue, but nab-paclitaxel and SPARC distributions were minimally correlated in either SPARC-positive or-negative animals. Nab-paclitaxel treatment neither decreased tumor stroma nor increased tumor vascular perfusion in either PDX model when compared with control groups. These data suggest that the specific tumor delivery of nab-paclitaxel is not directly related to SPARC expression, and nab-paclitaxel does not deplete tumor stroma in general.
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    Author List

  • Kim H; Samuel S; Lopez-Casas P; Grizzle W; Hidalgo M; Kovar J; Oelschlager D; Zinn K; Warram J; Buchsbaum D
  • Start Page

  • 680
  • End Page

  • 688
  • Volume

  • 15
  • Issue

  • 4