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19.04.2018 | Pancreatic Tumors | Ausgabe 7/2018

Annals of Surgical Oncology 7/2018

Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 7/2018
Autoren:
MD Yosuke Mukai, MD, PhD Daisaku Yamada, MD, PhD Hidetoshi Eguchi, MD, PhD Yoshifumi Iwagami, MD, PhD Tadafumi Asaoka, MD, PhD Takehiro Noda, MD, PhD Koichi Kawamoto, MD, PhD Kunihito Gotoh, MD, PhD Shogo Kobayashi, MD, PhD Yutaka Takeda, MD, PhD Masahiro Tanemura, MD, PhD Masaki Mori, MD, PhD Yuichiro Doki
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1245/​s10434-018-6431-8) contains supplementary material, which is available to authorized users.

Abstract

Background

The cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) are well known to play a dominant role in distant metastasis. Nevertheless, the effect on CAFs with current chemoradiation therapies remains uncertain.

Objective

This study aimed to reveal the role of CAFs under current chemoradiation therapy (CRT) and investigate the factors regulating CAFs.

Methods

α-SMA-positive cells in 86 resected PDAC specimens with/without preoperative CRT were evaluated by immunohistochemistry. Various factors, including the plasma levels of vitamin D, were investigated for association with the number of CAFs or distant metastasis-free survival (DMFS). Human pancreatic satellite cells (hPSCs) extracted from clinical specimens were used to validate the factors.

Results

All PDAC samples contained CAFs but the number varied widely. Multivariate analysis for DMFS indicated a larger number of CAFs was a significant risk factor. Univariate analysis for the number of CAFs identified two clinical factors: preoperative CRT and lower plasma levels of vitamin D. In subgroup analysis, the higher plasma level of vitamin D was a dominant factor for longer DMFS in PDAC patients after preoperative CRT. These results were validated by using extracted hPSCs. Irradiation activated stromal cells into CAFs facilitating malignant characteristics of PDAC and the change was inhibited by vitamin D supplementation in vitro.

Conclusion

In conjunction with established current therapies, vitamin D supplementation may be an effective treatment for PDAC patients by inactivating CAFs.

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Zusatzmaterial
Supplementary material 1 (DOCX 25 kb)
10434_2018_6431_MOESM1_ESM.docx
Supplementary material 2 (DOCX 17 kb)
10434_2018_6431_MOESM2_ESM.docx
Supplementary material 3 (PPTX 12704 kb)
10434_2018_6431_MOESM3_ESM.pptx
Literatur
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