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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Metastasis | Research

Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1

Authors: Tianzhu Lv, Hongjing Liu, Ling Mao, Yanrong Song, Lili Liao, Kun Zhong, Binbin Shuai, Yingkun Luo, Tingting Guo, Wentao Huang, Shenyingjie Zhang

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms.

Methods

CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1).

Results

CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo.

Conclusion

CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.
Appendix
Available only for authorised users
Literature
1.
Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, et al. Overview of oral cavity squamous cell carcinoma: risk factors, mechanisms, and diagnostics. Oral Oncol. 2021;121:105451.CrossRefPubMed
2.
Thomson PJ. Perspectives on oral squamous cell carcinoma prevention-proliferation, position, progression, and prediction. J Oral Pathol Med. 2018;47(9):803–7.CrossRefPubMed
3.
Law ZJ, Khoo XH, Lim PT, Goh BH, Ming LC, Lee WL, et al. Extracellular vesicle-mediated chemoresistance in oral squamous cell carcinoma. Front Mol Biosci. 2021;8:629888.CrossRefPubMedPubMedCentral
4.
Li H, Zhang Y, Xu M, Yang D. Current trends of targeted therapy for oral squamous cell carcinoma. J Cancer Res Clin Oncol. 2022;148(9):2169–86.CrossRefPubMed
5.
Zhang Y, Liu J, Liu S, Yu L, Liu S, Li M, et al. Extracellular vesicles in oral squamous cell carcinoma: current progress and future prospect. Front Bioeng Biotechnol. 2023;11:1149662.CrossRefPubMedPubMedCentral
6.
Naito Y, Yoshioka Y, Ochiya T. Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via extracellular vesicles. Cancer Cell Int. 2022;22(1):367.CrossRefPubMedPubMedCentral
7.
Shoucair I, Weber Mello F, Jabalee J, Maleki S, Garnis C. The role of Cancer-Associated fibroblasts and extracellular vesicles in Tumorigenesis. Int J Mol Sci 2020, 21(18).
8.
Dourado MR, Korvala J, Astrom P, De Oliveira CE, Cervigne NK, Mofatto LS, et al. Extracellular vesicles derived from cancer-associated fibroblasts induce the migration and invasion of oral squamous cell carcinoma. J Extracell Vesicles. 2019;8(1):1578525.CrossRefPubMedPubMedCentral
9.
Li YY, Tao YW, Gao S, Li P, Zheng JM, Zhang SE et al. Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine. 2018, 36:209–220.
10.
Sun LP, Xu K, Cui J, Yuan DY, Zou B, Li J, et al. Cancer–associated fibroblast–derived exosomal miR–382–5p promotes the migration and invasion of oral squamous cell carcinoma. Oncol Rep. 2019;42(4):1319–28.PubMedPubMedCentral
11.
Zhao Y, Yang W, Zheng K, Chen J, Jin X. The role of BMI1 in endometrial cancer and other cancers. Gene. 2023;856:147129.CrossRefPubMed
12.
Sun Q, Zhou C, Ma R, Guo Q, Huang H, Hao J, et al. Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis. Onco Targets Ther. 2018;11:1787–99.CrossRefPubMedPubMedCentral
13.
Custodio M, Biddle A, Tavassoli M. Portrait of a CAF: the story of cancer-associated fibroblasts in head and neck cancer. Oral Oncol. 2020;110:104972.CrossRefPubMed
14.
Hu C, Huang Q, Sun Q. The regulation of Lymph Node Pre-metastatic Niche formation in Head and Neck squamous cell carcinoma. Front Oncol. 2022;12:852611.CrossRefPubMedPubMedCentral
15.
Dourado MR, Guerra ENS, Salo T, Lambert DW, Coletta RD. Prognostic value of the immunohistochemical detection of cancer-associated fibroblasts in oral cancer: a systematic review and meta-analysis. J Oral Pathol Med. 2018;47(5):443–53.CrossRefPubMed
16.
Urabe F, Kosaka N, Ito K, Kimura T, Egawa S, Ochiya T. Extracellular vesicles as biomarkers and therapeutic targets for cancer. Am J Physiol Cell Physiol. 2020;318(1):C29–C39.CrossRefPubMed
17.
Chernova T, Grosso S, Sun XM, Tenor AR, Cabeza JZ, Craxton A et al. Extracellular vesicles isolated from malignant Mesothelioma Cancer-Associated fibroblasts induce pro-oncogenic changes in healthy mesothelial cells. Int J Mol Sci 2022, 23(20).
18.
Yang K, Zhang J, Bao C. Exosomal circEIF3K from cancer-associated fibroblast promotes colorectal cancer (CRC) progression via miR-214/PD-L1 axis. BMC Cancer. 2021;21(1):933.CrossRefPubMedPubMedCentral
19.
Zhang X, Wang Y, Wang X, Zou B, Mei J, Peng X, et al. Extracellular vesicles-encapsulated microRNA-10a-5p shed from cancer-associated fibroblast facilitates cervical squamous cell carcinoma cell angiogenesis and tumorigenicity via hedgehog signaling pathway. Cancer Gene Ther. 2021;28(5):529–42.CrossRefPubMed
20.
Uchihara T, Miyake K, Yonemura A, Komohara Y, Itoyama R, Koiwa M, et al. Extracellular vesicles from Cancer-Associated fibroblasts containing annexin A6 induces FAK-YAP activation by stabilizing beta1 integrin, enhancing Drug Resistance. Cancer Res. 2020;80(16):3222–35.CrossRefPubMed
21.
Chen C, Yang C, Tian X, Liang Y, Wang S, Wang X, et al. Downregulation of mir-100-5p in cancer-associated fibroblast-derived exosomes facilitates lymphangiogenesis in esophageal squamous cell carcinoma. Cancer Med. 2023;12(13):14468–83.CrossRefPubMedPubMedCentral
22.
23.
Kim SI, Woo SR, Noh JK, Lee MK, Lee YC, Lee JW, et al. Association between cancer stem cell gene expression signatures and prognosis in head and neck squamous cell carcinoma. BMC Cancer. 2022;22(1):1077.CrossRefPubMedPubMedCentral
24.
Kurihara K, Isobe T, Yamamoto G, Tanaka Y, Katakura A, Tachikawa T. Expression of BMI1 and ZEB1 in epithelial-mesenchymal transition of tongue squamous cell carcinoma. Oncol Rep. 2015;34(2):771–8.CrossRefPubMed
25.
Li Z, Wang Y, Yuan C, Zhu Y, Qiu J, Zhang W, et al. Oncogenic roles of Bmi1 and its therapeutic inhibition by histone deacetylase inhibitor in tongue cancer. Lab Invest. 2014;94(12):1431–45.CrossRefPubMed
26.
Liu L, Wu Y, Li Q, Liang J, He Q, Zhao L, et al. METTL3 promotes tumorigenesis and metastasis through BMI1 m(6)a methylation in oral squamous cell carcinoma. Mol Ther. 2020;28(10):2177–90.CrossRefPubMedPubMedCentral
27.
Liu Z, Hu C, Zheng L, Liu J, Li K, Li X, et al. BMI1 promotes cholangiocarcinoma progression and correlates with antitumor immunity in an exosome-dependent manner. Cell Mol Life Sci. 2022;79(9):469.CrossRefPubMed
28.
Iwatate Y, Yokota H, Hoshino I, Ishige F, Kuwayama N, Itami M, et al. Transcriptomic analysis reveals high ITGB1 expression as a predictor for poor prognosis of pancreatic cancer. PLoS ONE. 2022;17(6):e0268630.CrossRefPubMedPubMedCentral
29.
Li X, Dai Z, Wu X, Zhang N, Zhang H, Wang Z, et al. The Comprehensive Analysis identified an Autophagy signature for the prognosis and the Immunotherapy Efficiency Prediction in Lung Adenocarcinoma. Front Immunol. 2022;13:749241.CrossRefPubMedPubMedCentral
30.
Gu W, Sun H, Zhang M, Mo S, Tan C, Ni S, et al. ITGB1 as a prognostic biomarker correlated with immune suppression in gastric cancer. Cancer Med. 2023;12(2):1520–31.CrossRefPubMed
31.
Takahara T, Kasamatsu A, Yamatoji M, Iyoda M, Kasama H, Saito T, et al. SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7. Exp Cell Res. 2017;352(2):357–63.CrossRefPubMed
32.
Sun R, Yuan L, Jiang Y, Wan Y, Ma X, Yang J, et al. ALKBH5 activates FAK signaling through m6A demethylation in ITGB1 mRNA and enhances tumor-associated lymphangiogenesis and lymph node metastasis in ovarian cancer. Theranostics. 2023;13(2):833–48.CrossRefPubMedPubMedCentral
Metadata
Title
Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1
Authors
Tianzhu Lv
Hongjing Liu
Ling Mao
Yanrong Song
Lili Liao
Kun Zhong
Binbin Shuai
Yingkun Luo
Tingting Guo
Wentao Huang
Shenyingjie Zhang
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Metastasis
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11855-0

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