Extracelluar matrix metalloproteinase as a novel target for pancreatic cancer therapy.

Academic Article

Abstract

  • The objective of this study was to evaluate extracellular matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, whereas MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, whereas the other groups served as the control. In the residual tumor model, tumor growth of anti-EMMPRIN-treated group was successfully arrested for 21 days (15 ± 4 mm(3)), which was significantly lower than that of the EMMPRIN knockdown group (80 ± 15 mm(3); P=0.001) or the control group (240 ± 41 mm(3); P<0.001). In the established tumor model, anti-EMMPRIN therapy lowered tumor volume increase by approximately 40% compared with the control, regardless of the dose amount. Ki67-expressed cell density of group 5 was 939 ± 150 mm(-2), which was significantly lower than that of group 4 (1709 ± 145 mm(-2); P=0.006). Microvessel density of group 5 (30 ± 6 mm(-2)) was also significantly lower than that of group 4 (53 ± 5 mm(-2); P=0.014), whereas the microvessel size of group 5 (191 ± 22 μm(2)) was significantly larger than that of group 4 (113 ± 26 μm(2); P=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer and support its clinical translation.
  • Published In

  • Anti-Cancer Drugs  Journal
  • Keywords

  • Animals, Antibodies, Anti-Idiotypic, Antibodies, Monoclonal, Murine-Derived, Basigin, Cell Line, Tumor, Drug Evaluation, Preclinical, Extracellular Matrix, Female, Gene Knockdown Techniques, Humans, Ki-67 Antigen, Matrix Metalloproteinases, Mice, Mice, Inbred BALB C, Mice, SCID, Molecular Targeted Therapy, Pancreatic Neoplasms, Radioimmunoassay, Tumor Burden, Xenograft Model Antitumor Assays
  • Digital Object Identifier (doi)

    Author List

  • Kim H; Zhai G; Liu Z; Samuel S; Shah N; Helman EE; Knowles JA; Stockard CR; Fineberg NS; Grizzle WE
  • Start Page

  • 864
  • End Page

  • 874
  • Volume

  • 22
  • Issue

  • 9