Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Pro-tumoral behavior of omental adipocyte-derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer

Iyoshi, Shohei ; Yoshihara, Masato ; Nakamura, Kae ; Sugiyama, Mai ; Koya, Yoshihiro ; Kitami, Kazuhisa ; Uno, Kaname LU orcid ; Mogi, Kazumasa ; Tano, Sho and Tomita, Hiroyuki , et al. (2021) In International Journal of Cancer 149(11). p.1961-1972
Abstract

Adipocyte-rich omentum offers “good soil” for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt... (More)

Adipocyte-rich omentum offers “good soil” for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adipocyte, dedifferentiation, ovarian cancer, tumor microenvironment
in
International Journal of Cancer
volume
149
issue
11
pages
1961 - 1972
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85115075889
  • pmid:34469585
ISSN
0020-7136
DOI
10.1002/ijc.33770
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 UICC.
id
1c6363ee-607f-495c-a4e8-ce8710684d4f
date added to LUP
2021-10-13 14:00:47
date last changed
2024-06-15 18:02:10
@article{1c6363ee-607f-495c-a4e8-ce8710684d4f,
  abstract     = {{<p>Adipocyte-rich omentum offers “good soil” for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.</p>}},
  author       = {{Iyoshi, Shohei and Yoshihara, Masato and Nakamura, Kae and Sugiyama, Mai and Koya, Yoshihiro and Kitami, Kazuhisa and Uno, Kaname and Mogi, Kazumasa and Tano, Sho and Tomita, Hiroyuki and Kajiwara, Keiji and Taki, Masayasu and Yamaguchi, Shigehiro and Nawa, Akihiro and Kajiyama, Hiroaki}},
  issn         = {{0020-7136}},
  keywords     = {{adipocyte; dedifferentiation; ovarian cancer; tumor microenvironment}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1961--1972}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Pro-tumoral behavior of omental adipocyte-derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer}},
  url          = {{http://dx.doi.org/10.1002/ijc.33770}},
  doi          = {{10.1002/ijc.33770}},
  volume       = {{149}},
  year         = {{2021}},
}