Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling

Abstract Background The high potential for tumor recurrence and chemoresistance is a major challenge of clinical gastric cancer treatment. Increasing evidence suggests that the presence of tumor initiating cells (TICs) is the principal cause of tumor recurrence and chemoresistance. However, the unde...

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Autores principales:	Shuangya Deng, Lun Li, Shu Xu, Xiaobo Wang, Tong Han
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Tumor initiating cells (TICs) Collagen Integrin β1 signaling Y-box binding protein 1 (YBX1) Secreted phosphoprotein 1 (SPP1) Gastric cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/9e0f899313784e1e85aba656e6eb9c2c
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spelling	oai:doaj.org-article:9e0f899313784e1e85aba656e6eb9c2c2021-11-14T12:37:39ZPromotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling10.1186/s12935-021-02307-x1475-2867https://doaj.org/article/9e0f899313784e1e85aba656e6eb9c2c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02307-xhttps://doaj.org/toc/1475-2867Abstract Background The high potential for tumor recurrence and chemoresistance is a major challenge of clinical gastric cancer treatment. Increasing evidence suggests that the presence of tumor initiating cells (TICs) is the principal cause of tumor recurrence and chemoresistance. However, the underlying mechanism of TIC development remains controversial. Methods To identify novel molecular pathways in gastric cancer, we screened the genomic expression profile of 155 gastric cancer patients from the TCGA database. We then described an improved 3D collagen I gels and tested the effects of collagen on the TIC phenotype of gastric cells using colony formation assay, transwell assay, and nude mouse models. Additionally, cell apoptosis assay was performed to examine the cytotoxicity of 5-fluorine and paclitaxel on gastric cancer cells cultured in 3D collagen I gels. Results Elevated expression of type I collagen was observed in tumor tissues from high stage patients (stage T3–T4) when compared to the low stage group (n=10, stage T1–T2). Furthermore, tumor cells seeded in a low concentration of collagen gels acquired TIC-like phenotypes and revealed enhanced resistance to chemotherapeutic agents, which was dependent on an integrin β1 (ITGB1)/Y-box Binding Protein 1 (YBX1)/Secreted Phosphoprotein 1 (SPP1)/NF-κB signaling pathway. Importantly, inhibition of ITGB1/NF-κB signaling efficiently reversed the chemoresistance induced by collagen and promoted anticancer effects in vivo. Conclusions Our findings demonstrated that type I collagen promoted TIC-like phenotypes and chemoresistance through ITGB1/YBX1/SPP1/NF-κB pathway, which may provide novel insights into gastric cancer therapy.Shuangya DengLun LiShu XuXiaobo WangTong HanBMCarticleTumor initiating cells (TICs)CollagenIntegrin β1 signalingY-box binding protein 1 (YBX1)Secreted phosphoprotein 1 (SPP1)Gastric cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tumor initiating cells (TICs) Collagen Integrin β1 signaling Y-box binding protein 1 (YBX1) Secreted phosphoprotein 1 (SPP1) Gastric cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Tumor initiating cells (TICs) Collagen Integrin β1 signaling Y-box binding protein 1 (YBX1) Secreted phosphoprotein 1 (SPP1) Gastric cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Shuangya Deng Lun Li Shu Xu Xiaobo Wang Tong Han Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling
description	Abstract Background The high potential for tumor recurrence and chemoresistance is a major challenge of clinical gastric cancer treatment. Increasing evidence suggests that the presence of tumor initiating cells (TICs) is the principal cause of tumor recurrence and chemoresistance. However, the underlying mechanism of TIC development remains controversial. Methods To identify novel molecular pathways in gastric cancer, we screened the genomic expression profile of 155 gastric cancer patients from the TCGA database. We then described an improved 3D collagen I gels and tested the effects of collagen on the TIC phenotype of gastric cells using colony formation assay, transwell assay, and nude mouse models. Additionally, cell apoptosis assay was performed to examine the cytotoxicity of 5-fluorine and paclitaxel on gastric cancer cells cultured in 3D collagen I gels. Results Elevated expression of type I collagen was observed in tumor tissues from high stage patients (stage T3–T4) when compared to the low stage group (n=10, stage T1–T2). Furthermore, tumor cells seeded in a low concentration of collagen gels acquired TIC-like phenotypes and revealed enhanced resistance to chemotherapeutic agents, which was dependent on an integrin β1 (ITGB1)/Y-box Binding Protein 1 (YBX1)/Secreted Phosphoprotein 1 (SPP1)/NF-κB signaling pathway. Importantly, inhibition of ITGB1/NF-κB signaling efficiently reversed the chemoresistance induced by collagen and promoted anticancer effects in vivo. Conclusions Our findings demonstrated that type I collagen promoted TIC-like phenotypes and chemoresistance through ITGB1/YBX1/SPP1/NF-κB pathway, which may provide novel insights into gastric cancer therapy.
format	article
author	Shuangya Deng Lun Li Shu Xu Xiaobo Wang Tong Han
author_facet	Shuangya Deng Lun Li Shu Xu Xiaobo Wang Tong Han
author_sort	Shuangya Deng
title	Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling
title_short	Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling
title_full	Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling
title_fullStr	Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling
title_full_unstemmed	Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling
title_sort	promotion of gastric tumor initiating cells in a 3d collagen gel culture model via ybx1/spp1/nf-κb signaling
publisher	BMC
publishDate	2021
url	https://doaj.org/article/9e0f899313784e1e85aba656e6eb9c2c
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Promotion of gastric tumor initiating cells in a 3D collagen gel culture model via YBX1/SPP1/NF-κB signaling

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