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Peritoneal restorat...
Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination via blockade of the TGF-β1/thrombospondin-1 axis
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- Kitami, Kazuhisa (author)
- Nagoya University
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- Yoshihara, Masato (author)
- Nagoya University
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- Tamauchi, Satoshi (author)
- Nagoya University
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- Sugiyama, Mai (author)
- Nagoya University
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- Koya, Yoshihiro (author)
- Nagoya University
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- Yamakita, Yoshihiko (author)
- Nagoya University
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- Fujimoto, Hiroki (author)
- Nagoya University
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- Iyoshi, Shohei (author)
- Albert-Ludwigs University Freiburg,Nagoya University
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- Uno, Kaname (author)
- Lund 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
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- Mogi, Kazumasa (author)
- Nagoya University
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- Ikeda, Yoshiki (author)
- Nagoya University
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- Yokoi, Akira (author)
- Nagoya University
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- Yoshikawa, Nobuhisa (author)
- Nagoya University
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- Nishino, Kimihiro (author)
- Nagoya University
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- Niimi, Kaoru (author)
- Nagoya University
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- Nawa, Akihiro (author)
- Nagoya University
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- Enomoto, Atsushi (author)
- Nagoya University
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- Kajiyama, Hiroaki (author)
- Nagoya University
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English 21 s.
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In: Matrix Biology. - : Elsevier BV. - 0945-053X. ; 109, s. 70-90
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- Ovarian cancer (OvCa), a lethal gynecological malignancy, disseminates to the peritoneum. Mesothelial cells (MCs) act as barriers in the abdominal cavity, preventing the adhesion of cancer cells. However, in patients with OvCa, they are transformed into cancer-associated mesothelial cells (CAMs) via mesenchymal transition and form a favorable microenvironment for tumors to promote metastasis. However, attempts for restoring CAMs to their original state have been limited. Here, we investigated whether inhibition of mesenchymal transition and restoration of MCs by vitamin D suppressed the OvCa dissemination in vitro and in vivo. The effect of vitamin D on the mutual association of MCs and OvCa cells was evaluated using in vitro coculture models and in vivo using a xenograft model. Vitamin D restored the CAMs, and thrombospondin-1 (component of the extracellular matrix that is clinically associated with poor prognosis and is highly expressed in peritoneally metastasized OvCa) was found to promote OvCa cell adhesion and proliferation. Mechanistically, TGF-β1 secreted from OvCa cells enhanced thrombospondin-1 expression in CAMs via Smad-dependent TGF-β signaling. Vitamin D inhibited mesenchymal transition in MCs and suppressed thrombospondin-1 expression via vitamin D receptor/Smad3 competition, contributing to the marked reduction in peritoneal dissemination in vivo. Importantly, vitamin D restored CAMs from a stabilized mesenchymal state to the epithelial state and normalized thrombospondin-1 expression in preclinical models that mimic cancerous peritonitis in vivo. MCs are key players in OvCa dissemination and peritoneal restoration and normalization of thrombospondin-1 expression by vitamin D may be a novel strategy for preventing OvCa dissemination.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Epithelial-mesenchymal transition (EMT)
- Metastasis
- Ovarian cancer
- Peritoneum
- Thrombospondin-1
- Vitamin D
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Kitami, Kazuhisa
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Yoshihara, Masat ...
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Tamauchi, Satosh ...
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Sugiyama, Mai
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Koya, Yoshihiro
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Yamakita, Yoshih ...
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show more...
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Fujimoto, Hiroki
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Iyoshi, Shohei
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Uno, Kaname
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Mogi, Kazumasa
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Ikeda, Yoshiki
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Yokoi, Akira
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Yoshikawa, Nobuh ...
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Nishino, Kimihir ...
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Niimi, Kaoru
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Nawa, Akihiro
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Enomoto, Atsushi
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Kajiyama, Hiroak ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Matrix Biology
- By the university
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Lund University