Neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel reduces the number of cancer-associated fibroblasts through depletion of pancreatic stroma

Tomoharu Miyashita, Hidehiro Tajima, Isamu Makino, Mitsuyoshi Okazaki, Takahisa Yamaguchi, Yoshinao Ohbatake, Sinichi Nakanuma, Hironori Hayashi, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Koji Kishimoto, John W. Harmon, Tetsuo Ohta

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In this study, the effects of neoadjuvant chemotherapy (NAC) on cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma were investigated. Materials and Methods: Density of a-smooth muscle actin (aSMA)-positive fibroblasts in resected surgical specimens from untreated patients, patients receiving conventional gemcitabine plus S-1 (GS), and patients receiving gemcitabine plus nab-paclitaxel (GnP) was determined by hybrid cell counting. 18F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) scans and carbohydrate antigen 19-9 (CA19-9) concentrations were used to assess tumor activity before and after chemotherapy in the GnP group. Results: In this retrospective study of 65 patients, aSMA expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of aSMA-positive fibroblasts. There were significantly fewer aSMA-positive fibroblasts in the GnP than in the untreated and GS groups, but there was no significant difference between the latter two groups. aSMA density reflected a decrease in standardized uptake value on FDG-PET, but not CA19-9 concentration, after GnP chemotherapy. Conclusion: These data suggest that the GnP regimen induces stromal depletion, resulting in fewer CAFs.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalAnticancer research
Volume38
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • Cancer-associated fibroblast
  • Chemoresistance
  • Pancreatic cancer
  • Stroma
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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