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Annals of Surgical Oncology

, Volume 26, Issue 5, pp 1552–1559 | Cite as

Cellular Senescence, Represented by Expression of Caveolin-1, in Cancer-Associated Fibroblasts Promotes Tumor Invasion in Pancreatic Cancer

  • Takanobu Yamao
  • Yo-ichi Yamashita
  • Kensuke Yamamura
  • Yosuke Nakao
  • Masayo Tsukamoto
  • Shigeki Nakagawa
  • Hirohisa Okabe
  • Hiromitsu Hayashi
  • Katsunori Imai
  • Hideo BabaEmail author
Translational Research and Biomarkers
  • 158 Downloads

Abstract

Background

The role of senescence of cancer-associated fibroblasts (CAFs) in the development of cancer is controversial. In this study, we investigated whether cellular senescence of CAFs, represented by CAV1 expression, affects tumor progression in pancreatic cancers (PC).

Methods

Because CAV1 plays a major role in cellular senescence, we used CAV1 expression to monitor cellular senescence. A total of 157 consecutive patients with PC who underwent curative resection were enrolled in the study. Patients were divided into two groups according to CAV1 expression in CAFs by immunohistochemistry. We investigated the relationship between the CAV1 expression in CAFs and the patients’ clinicopathological characteristics, including survival. We also established ten CAFs cell lines using PC clinical samples and chose one of them to knock down CAV1 expression. Finally, we cultured a PC cell line (MIAPaCa-2) in CAF-conditioned medium (CM).

Results

Regarding patients’ clinicopathological characteristics, the serum levels of carbohydrate antigen 19-9 and the rate of advanced tumor stage (pT2, 3, and 4) were significantly higher in the high-CAV1 group. The high-CAV1 group had significantly worse outcomes in both overall and disease-free survival (p < 0.01). Additionally, in co-culture assays using CAFs-CM and MIAPaCa-2 cells, we found that knockdown of CAV1 in CAFs negatively affected the invasion of PC cells.

Conclusions

In PC, CAV1 expression in CAFs is associated with patients’ poor prognosis and the downregulation of CAV1 in CAFs reduces the invasiveness of PC cells. Therefore, CAV1 of CAFs might be a new target for the treatment of PC.

Notes

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10434_2019_7266_MOESM1_ESM.docx (372 kb)
Supplementary material 1 (DOCX 372 kb)

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Takanobu Yamao
    • 1
  • Yo-ichi Yamashita
    • 1
  • Kensuke Yamamura
    • 1
  • Yosuke Nakao
    • 1
  • Masayo Tsukamoto
    • 1
  • Shigeki Nakagawa
    • 1
  • Hirohisa Okabe
    • 1
  • Hiromitsu Hayashi
    • 1
  • Katsunori Imai
    • 1
  • Hideo Baba
    • 1
    • 2
    Email author
  1. 1.Department of Gastroenterological Surgery, Graduate School of Life SciencesKumamoto UniversityKumamotoJapan
  2. 2.Center for Metabolic Regulation of Healthy AgingKumamoto University Faculty of Life SciencesKumamotoJapan

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