Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5

Adipose‐derived stem cells (ADSCs) play a vital role in colorectal cancer (CRC) progression, but the mechanism remains largely unknown. Herein, we found that ADSCs isolated from CRC patients produced more cysteine‐rich 61 (Cyr61) than those from healthy donors, and the elevated serum Cyr61 levels we...

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Autores principales:	Zhenxing Liang, Huashan Liu, Yunfeng Zhang, Li Xiong, Ziwei Zeng, Xiaowen He, Fengwei Wang, Xianrui Wu, Ping Lan
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	adipose‐derived stem cells colorectal cancer Cyr61 metastasis and vasculogenic mimicry formation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/420d3329c2b04b3dadfdd1a1aac7f0ed
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spelling	oai:doaj.org-article:420d3329c2b04b3dadfdd1a1aac7f0ed2021-12-02T10:31:06ZCyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ51878-02611574-789110.1002/1878-0261.12998https://doaj.org/article/420d3329c2b04b3dadfdd1a1aac7f0ed2021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.12998https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Adipose‐derived stem cells (ADSCs) play a vital role in colorectal cancer (CRC) progression, but the mechanism remains largely unknown. Herein, we found that ADSCs isolated from CRC patients produced more cysteine‐rich 61 (Cyr61) than those from healthy donors, and the elevated serum Cyr61 levels were associated with advanced TNM stages. Moreover, serum Cyr61 displayed a better diagnostic value for CRC compared to carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19‐9). Mechanistically, integrin αVβ5 was identified as the functional receptor by which Cyr61 promotes CRC cell metastasis in vitro and in vivo by activating the αVβ5/FAK/NF‐κB signaling pathway. In addition, Cyr61 promotes vasculogenic mimicry (VM) formation, thereby promoting tumor growth and metastasis through a αVβ5/FAK/HIF‐1α/STAT3/MMP2 signaling cascade. Histologically, xenografts and clinical samples of CRC both exhibited VM, which was correlated with HIF‐1α and MMP2 activation. Notably, we demonstrated the synergistic effect of combined anti‐VM therapy (integrin αVβ5 inhibitor) and anti‐VEGF therapy (bevacizumab) in patient‐derived xenograft models. Further investigation showed that CRC cell‐derived exosomal STAT3 promoted Cyr61 transcription in ADSCs. These findings indicate that Cyr61 derived from ADSCs plays a critical role in promoting CRC progression via integrin αVβ5 and provides a novel antitumor strategy by targeting Cyr61/αVβ5.Zhenxing LiangHuashan LiuYunfeng ZhangLi XiongZiwei ZengXiaowen HeFengwei WangXianrui WuPing LanWileyarticleadipose‐derived stem cellscolorectal cancerCyr61metastasis and vasculogenic mimicry formationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3447-3467 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adipose‐derived stem cells colorectal cancer Cyr61 metastasis and vasculogenic mimicry formation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	adipose‐derived stem cells colorectal cancer Cyr61 metastasis and vasculogenic mimicry formation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhenxing Liang Huashan Liu Yunfeng Zhang Li Xiong Ziwei Zeng Xiaowen He Fengwei Wang Xianrui Wu Ping Lan Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5
description	Adipose‐derived stem cells (ADSCs) play a vital role in colorectal cancer (CRC) progression, but the mechanism remains largely unknown. Herein, we found that ADSCs isolated from CRC patients produced more cysteine‐rich 61 (Cyr61) than those from healthy donors, and the elevated serum Cyr61 levels were associated with advanced TNM stages. Moreover, serum Cyr61 displayed a better diagnostic value for CRC compared to carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19‐9). Mechanistically, integrin αVβ5 was identified as the functional receptor by which Cyr61 promotes CRC cell metastasis in vitro and in vivo by activating the αVβ5/FAK/NF‐κB signaling pathway. In addition, Cyr61 promotes vasculogenic mimicry (VM) formation, thereby promoting tumor growth and metastasis through a αVβ5/FAK/HIF‐1α/STAT3/MMP2 signaling cascade. Histologically, xenografts and clinical samples of CRC both exhibited VM, which was correlated with HIF‐1α and MMP2 activation. Notably, we demonstrated the synergistic effect of combined anti‐VM therapy (integrin αVβ5 inhibitor) and anti‐VEGF therapy (bevacizumab) in patient‐derived xenograft models. Further investigation showed that CRC cell‐derived exosomal STAT3 promoted Cyr61 transcription in ADSCs. These findings indicate that Cyr61 derived from ADSCs plays a critical role in promoting CRC progression via integrin αVβ5 and provides a novel antitumor strategy by targeting Cyr61/αVβ5.
format	article
author	Zhenxing Liang Huashan Liu Yunfeng Zhang Li Xiong Ziwei Zeng Xiaowen He Fengwei Wang Xianrui Wu Ping Lan
author_facet	Zhenxing Liang Huashan Liu Yunfeng Zhang Li Xiong Ziwei Zeng Xiaowen He Fengwei Wang Xianrui Wu Ping Lan
author_sort	Zhenxing Liang
title	Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5
title_short	Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5
title_full	Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5
title_fullStr	Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5
title_full_unstemmed	Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5
title_sort	cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αvβ5
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/420d3329c2b04b3dadfdd1a1aac7f0ed
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Cyr61 from adipose‐derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αVβ5

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