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

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.

Yoshihara, MasatoNagoya University (author)
Nakamura, KaeNagoya University (author)
Sugiyama, MaiNagoya University (author)
Koya, YoshihiroNagoya University (author)
Kitami, KazuhisaNagoya University (author)
Uno, KanameLund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Nagoya University(Swepub:lu)ka6202un (author)
Mogi, KazumasaNagoya University (author)
Tano, ShoNagoya University (author)
Tomita, HiroyukiGifu University (author)
Kajiwara, KeijiNagoya University (author)
Taki, MasayasuNagoya University (author)
Yamaguchi, ShigehiroNagoya University (author)
Nawa, AkihiroNagoya University (author)
Kajiyama, HiroakiNagoya University (author)
Albert-Ludwigs University FreiburgNagoya University (creator_code:org_t)

By the author/editor: Iyoshi, Shohei; Yoshihara, Masat ...; Nakamura, Kae; Sugiyama, Mai; Koya, Yoshihiro; Kitami, Kazuhisa; show more...; Uno, Kaname; Mogi, Kazumasa; Tano, Sho; Tomita, Hiroyuki; Kajiwara, Keiji; Taki, Masayasu; Yamaguchi, Shige ...; Nawa, Akihiro; Kajiyama, Hiroak ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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