Cancer-Associated Fibroblast-Secreted Exosomes Promote Gastric Cancer Cell Migration and Invasion Via the IL-32/ESR1 Axis

Overview

Journal Appl Biochem Biotechnol

Specialties Biochemistry
Biotechnology

Date 2024 Jan 5

PMID 38180644

Authors

Lifeng Shang

Xinli Chen

Tianyu Zhu

Shujing Chong

Haiwang Liu

Wei Huang

Weibo Fu

Hao She

Xin Shen

Affiliations

Soon will be listed here.

Abstract

Exosomes secreted by cancer-associated fibroblasts (CAFs) play a critical part in cancer progression. This study aimed to explore the effects of CAF-exosomes on gastric cancer (GC) cell metastasis. AGS and HGC-27 cells were treated with exosomes and cell viability, migration, and invasion were evaluated using Cell-Counting Kit-8 and Transwell assays. Exosome-regulated mRNAs were explored using quantitative real-time PCR. The relationship between interleukin (IL)32 and estrogen receptor 1 (ESR1) was evaluated using co-immunoprecipitation and dual-luciferase reporter assays. The results of this study show that CAF-derived exosomes promote GC cell viability, migration, and invasion. Exosome treatment increased the levels of IL32, which interacted with ESR1 and negatively regulated ESR1 levels. Rescue experiments were conducted to demonstrate that CAF-exosomes promoted biological behaviors of GC cells by upregulating IL32 and downregulating ESR1 expression. In conclusion, CAF-derived exosomes promote GC cell viability, migration, and invasion by elevating the IL32/ESR1 axis, suggesting a novel strategy for metastatic GC treatment.

Citing Articles

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Sun T, Song Q, Liu H Oncol Res. 2024; 33(1):133-148.

PMID: 39735680 PMC: 11671617. DOI: 10.32604/or.2024.054141.

References

Smyth E, Nilsson M, Grabsch H, van Grieken N, Lordick F . Gastric cancer. Lancet. 2020; 396(10251):635-648. DOI: 10.1016/S0140-6736(20)31288-5. View

Thrift A, El-Serag H . Burden of Gastric Cancer. Clin Gastroenterol Hepatol. 2019; 18(3):534-542. PMC: 8859863. DOI: 10.1016/j.cgh.2019.07.045. View

Sexton R, Al Hallak M, Diab M, Azmi A . Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer Metastasis Rev. 2020; 39(4):1179-1203. PMC: 7680370. DOI: 10.1007/s10555-020-09925-3. View

Biffi G, Tuveson D . Diversity and Biology of Cancer-Associated Fibroblasts. Physiol Rev. 2020; 101(1):147-176. PMC: 7864232. DOI: 10.1152/physrev.00048.2019. View

Ma Z, Chen M, Yang X, Xu B, Song Z, Zhou B . The Role of Cancer-associated Fibroblasts in Tumorigenesis of Gastric Cancer. Curr Pharm Des. 2018; 24(28):3297-3302. DOI: 10.2174/1381612824666180601094056. View

Chen Y, McAndrews K, Kalluri R . Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol. 2021; 18(12):792-804. PMC: 8791784. DOI: 10.1038/s41571-021-00546-5. View

Kalluri R, LeBleu V . The biology function and biomedical applications of exosomes. Science. 2020; 367(6478). PMC: 7717626. DOI: 10.1126/science.aau6977. View

Wortzel I, Dror S, Kenific C, Lyden D . Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell. 2019; 49(3):347-360. DOI: 10.1016/j.devcel.2019.04.011. View

Zhang L, Yu D . Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev Cancer. 2019; 1871(2):455-468. PMC: 6542596. DOI: 10.1016/j.bbcan.2019.04.004. View

10.

Yang X, Li Y, Zou L, Zhu Z . Role of Exosomes in Crosstalk Between Cancer-Associated Fibroblasts and Cancer Cells. Front Oncol. 2019; 9:356. PMC: 6510008. DOI: 10.3389/fonc.2019.00356. View

11.

Li C, Fonseca Teixeira A, Zhu H, Ten Dijke P . Cancer associated-fibroblast-derived exosomes in cancer progression. Mol Cancer. 2021; 20(1):154. PMC: 8638446. DOI: 10.1186/s12943-021-01463-y. View

12.

Chen B, Sang Y, Song X, Zhang D, Wang L, Zhao W . Exosomal miR-500a-5p derived from cancer-associated fibroblasts promotes breast cancer cell proliferation and metastasis through targeting USP28. Theranostics. 2021; 11(8):3932-3947. PMC: 7914354. DOI: 10.7150/thno.53412. View

13.

Li Y, Tao Y, Gao S, Li P, Zheng J, Zhang S . Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine. 2018; 36:209-220. PMC: 6197737. DOI: 10.1016/j.ebiom.2018.09.006. View

14.

Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D . CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020; 19(1):43. PMC: 7045485. DOI: 10.1186/s12943-020-01168-8. View

15.

Sun L, Huang C, Zhu M, Guo S, Gao Q, Wang Q . Gastric cancer mesenchymal stem cells regulate PD-L1-CTCF enhancing cancer stem cell-like properties and tumorigenesis. Theranostics. 2020; 10(26):11950-11962. PMC: 7667687. DOI: 10.7150/thno.49717. View

16.

Friedl P, Wolf K . Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003; 3(5):362-74. DOI: 10.1038/nrc1075. View

17.

Sun H, Wang X, Wang X, Xu M, Sheng W . The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer. Cell Death Dis. 2022; 13(10):874. PMC: 9573863. DOI: 10.1038/s41419-022-05320-8. View

18.

Mao X, Xu J, Wang W, Liang C, Hua J, Liu J . Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Mol Cancer. 2021; 20(1):131. PMC: 8504100. DOI: 10.1186/s12943-021-01428-1. View

19.

Seo N, Akiyoshi K, Shiku H . Exosome-mediated regulation of tumor immunology. Cancer Sci. 2018; 109(10):2998-3004. PMC: 6172045. DOI: 10.1111/cas.13735. View

20.

Richards K, Zeleniak A, Fishel M, Wu J, Littlepage L, Hill R . Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene. 2016; 36(13):1770-1778. PMC: 5366272. DOI: 10.1038/onc.2016.353. View