Impact of Extravasated Platelet Activation and Podoplanin-positive Cancer-associated Fibroblasts in Pancreatic Cancer Stroma.


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Oct 2019
Historique:
received: 25 08 2019
revised: 31 08 2019
accepted: 03 09 2019
entrez: 2 10 2019
pubmed: 2 10 2019
medline: 9 10 2019
Statut: ppublish

Résumé

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. 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). 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. 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.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 31570451
pii: 39/10/5565
doi: 10.21873/anticanres.13750
doi:

Substances chimiques

130-nm albumin-bound paclitaxel 0
Albumins 0
Drug Combinations 0
Membrane Glycoproteins 0
PDPN protein, human 0
Platelet Glycoprotein GPIb-IX Complex 0
Deoxycytidine 0W860991D6
S 1 (combination) 150863-82-4
Tegafur 1548R74NSZ
Oxonic Acid 5VT6420TIG
Paclitaxel P88XT4IS4D
Gemcitabine 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5565-5572

Informations de copyright

Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Tomoharu Miyashita (T)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan tomoharumiya@gmail.com.

Hidehiro Tajima (H)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Ryosuke Gabata (R)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Mitsuyoshi Okazaki (M)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Hiroyuki Shimbashi (H)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Yoshinao Ohbatake (Y)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Koichi Okamoto (K)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Sinichi Nakanuma (S)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Seisho Sakai (S)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Isamu Makino (I)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Jun Kinoshita (J)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Hironori Hayashi (H)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Keishi Nakamura (K)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Hiroyuki Takamura (H)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Itasu Ninomiya (I)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Sachio Fushida (S)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

John W Harmon (JW)

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.

Tetsuo Ohta (T)

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

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