SPARC-Independent Delivery of Nab-Paclitaxel without Depleting Tumor Stroma in Patient-Derived Pancreatic Cancer Xenografts.

Academic Article

Abstract

  • The study goal was to examine the relationship between nab-paclitaxel 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 IRDye 800CW (IR800)-labeled nab-paclitaxel. After 24 hours, tumors were collected and stained with DL650-labeled anti-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 (30 mg/kg body weight, i.v., for 5 consecutive days), and these agents in combination, respectively, for 3 weeks, and tumor volume and perfusion changes were assessed using T2-weighted MRI and dynamic contrast-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. Mol Cancer Ther; 15(4); 680-8. ©2016 AACR.
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    Keywords

  • Albumins, Animals, Antineoplastic Agents, Phytogenic, Deoxycytidine, Disease Models, Animal, Drug Synergism, Female, Humans, Mice, Microcirculation, Osteonectin, Paclitaxel, Pancreatic Neoplasms, Stromal Cells, Tumor Burden, Xenograft Model Antitumor Assays
  • Digital Object Identifier (doi)

    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