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

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgment

The authors thank the members of our laboratories for their helpful discussions. No external sources of funding were received for this study.

Disclosures

The authors have no commercial interests in the subject matter of this study.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan

    Yosuke Mukai MD, 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 MD, PhD

  2. Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan

    Yutaka Takeda MD, PhD

  3. Department of Surgery, Osaka Police Hospital, Tennoji, Japan

    Masahiro Tanemura MD, PhD

Authors
  1. Yosuke Mukai MD
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  2. Daisaku Yamada MD, PhD
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  3. Hidetoshi Eguchi MD, PhD
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  4. Yoshifumi Iwagami MD, PhD
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  5. Tadafumi Asaoka MD, PhD
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  6. Takehiro Noda MD, PhD
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  7. Koichi Kawamoto MD, PhD
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  8. Kunihito Gotoh MD, PhD
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  9. Shogo Kobayashi MD, PhD
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  10. Yutaka Takeda MD, PhD
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  11. Masahiro Tanemura MD, PhD
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  12. Masaki Mori MD, PhD
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  13. Yuichiro Doki MD, PhD
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Corresponding author

Correspondence to Hidetoshi Eguchi MD, PhD.

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Mukai, Y., Yamada, D., Eguchi, H. et al. Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy. Ann Surg Oncol 25, 1868–1879 (2018). https://doi.org/10.1245/s10434-018-6431-8

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  • DOI: https://doi.org/10.1245/s10434-018-6431-8

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