Impact of extravasated platelet activation and podoplanin-positive cancer-associated fibroblasts in pancreatic cancer stroma

Tomoharu Miyashita, Hidehiro Tajima, Ryosuke Gabata, Mitsuyoshi Okazaki, Hiroyuki Shimbashi, Yoshinao Ohbatake, Koichi Okamoto, Sinichi Nakanuma, Seisho Sakai, Isamu Makino, Jun Kinoshita, Hironori Hayashi, Keishi Nakamura, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, John Harmon, Tetsuo Ohta

Research output: Contribution to journalArticle

Abstract

Background/Aim: The aim of the study was to evaluate the status of extravasated platelet activation (EPA) surrounding podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma by neoadjuvant chemotherapy. Patients and Methods: A total of 74 patients were enrolled in this study. We investigated CD42b and PDPN expression in the groups of untreated, gemcitabine (GEM) alone, GEM plus S-1 (GS) and GEM plus nab-paclitaxel (GnP). Results: CD42b expression in surrounding CAFs was observed in 58% patients. CD42b expression was significantly correlated with PDPN expression. CD42b-positive cases were significantly lower in the group treated with GnP than in the untreated group and groups treated with GEM alone or GS. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN-positive fibroblasts. There was a significantly lower CD42b expression and fewer PDPN-positive fibroblasts in the GnP group than in untreated, GEM alone, and GS groups, but there was no significant difference between the latter three groups. Conclusion: There is a significant association between EPA and PDPN-positive CAFs in pancreatic cancer stroma. Our data suggest that the GnP regimen decreases EPA through PDPN-positive CAF depletion.

Original languageEnglish (US)
Pages (from-to)5565-5572
Number of pages8
JournalAnticancer Research
Volume39
Issue number10
DOIs
StatePublished - Jan 1 2019

Keywords

  • Cancer-associated fibroblast
  • Extravasated platelet activation
  • Neoadjuvant chemotherapy
  • Pancreatic cancer stroma
  • Podoplanin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Impact of extravasated platelet activation and podoplanin-positive cancer-associated fibroblasts in pancreatic cancer stroma'. Together they form a unique fingerprint.

  • Cite this

    Miyashita, T., Tajima, H., Gabata, R., Okazaki, M., Shimbashi, H., Ohbatake, Y., Okamoto, K., Nakanuma, S., Sakai, S., Makino, I., Kinoshita, J., Hayashi, H., Nakamura, K., Takamura, H., Ninomiya, I., Fushida, S., Harmon, J., & Ohta, T. (2019). Impact of extravasated platelet activation and podoplanin-positive cancer-associated fibroblasts in pancreatic cancer stroma. Anticancer Research, 39(10), 5565-5572. https://doi.org/10.21873/anticanres.13750