Pro-tumoral behavior of omental adipocyte-derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer
(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)
- author
- organization
- publishing date
- 2021
- 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
-
- pmid:34469585
- scopus:85115075889
- 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
- 2025-01-26 17:09:12
@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}}, }