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.
| Original language | English |
|---|---|
| Pages (from-to) | 1868-1879 |
| Number of pages | 12 |
| Journal | Annals of Surgical Oncology |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 1 2018 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Surgery
- Oncology
Cite this
Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy. / Mukai, Yosuke; Yamada, Daisaku; Eguchi, Hidetoshi; Iwagami, Yoshifumi; Asaoka, Tadafumi; Noda, Takehiro; Kawamoto, Koichi; Gotoh, Kunihito; Kobayashi, Shogo; Takeda, Yutaka; Tanemura, Masahiro; Mori, Masaki; Doki, Yuichiro.
In: Annals of Surgical Oncology, Vol. 25, No. 7, 01.07.2018, p. 1868-1879.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy
AU - Mukai, Yosuke
AU - Yamada, Daisaku
AU - Eguchi, Hidetoshi
AU - Iwagami, Yoshifumi
AU - Asaoka, Tadafumi
AU - Noda, Takehiro
AU - Kawamoto, Koichi
AU - Gotoh, Kunihito
AU - Kobayashi, Shogo
AU - Takeda, Yutaka
AU - Tanemura, Masahiro
AU - Mori, Masaki
AU - Doki, Yuichiro
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045741026&partnerID=8YFLogxK
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U2 - 10.1245/s10434-018-6431-8
DO - 10.1245/s10434-018-6431-8
M3 - Article
C2 - 29675761
AN - SCOPUS:85045741026
VL - 25
SP - 1868
EP - 1879
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
SN - 1068-9265
IS - 7
ER -