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

Yosuke Mukai, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Tadafumi Asaoka, Takehiro Noda, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki

研究成果: Contribution to journalArticle

7 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1868-1879
ページ数12
ジャーナルAnnals of Surgical Oncology
25
7
DOI
出版ステータス出版済み - 7 1 2018

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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