Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis

Abstract

Background: Intratumor heterogeneity is common in cancers, with different cell subtypes supporting each other to become more malignant. Nasopharyngeal carcinoma (NPC), a highly metastatic cancer, shows significant heterogeneity among its cells. This study investigates how NPC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules.

Methods: Exosomes were purified and characterized. MicroRNA expression was analyzed via sequencing and qRT-PCR. The effects of miR-30a-5p on migration, invasion, and metastasis were evaluated in vitro and in vivo. Its impact on desmoglein glycoprotein (DSG2) was assessed using dual-luciferase assays and Western blotting. Immunohistochemistry (IHC) and statistical models linked miR-30a-5p/DSG2 levels to patient prognosis.

Results: Different NPC cell subtypes transmit metastatic potential via exosomes. High-metastatic cells enhance the migration, invasion, and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p. Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis. miR-30a-5p may promote metastasis by targeting DSG2 and modulating Wnt signaling. Plasma exosomal miR-30a-5p inversely correlates with DSG2 levels, predicting patient outcomes.

Conclusion: High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p, which is a valuable prognostic marker assessable via liquid biopsy.

Keywords

cell heterogeneity / cell communication / exosomes / metastasis / nasopharyngeal carcinoma

Acknowledgement

This work was supported by grants from the National Key Research and Development Program of China (Grant Nos. 2022YFC2505800, 2022YFC2705005), the National Natural Science Foundation of China (Grant Nos. 32200651, 82203776, 82203125, 82222050, 82272739, 82272882, 82173287, 82073003, 82003267, 82002852), Guangdong Basic and Applied Basic Research Foundation (Grant Nos. 2021B1515230002, 2022A1515110033), Science and Technology Program of Guangzhou(Grant Nos. 202201011561, 2023A04J2127), Sun Yat-sen University Clinical Research 5010 Program (Grant Nos. 201315, 2015021, 2017010, 2019023), Innovative Research Team of High-level Local Universities in Shanghai (Grant No. SSMU-ZLCX20180500), Postdoctoral Innovative Talent Support Program (Grant No. BX20220361), Planned Science and Technology Project of Guangdong Province (Grant No. 2019B020230002), Key Youth Teacher Cultivating Program of Sun Yat-sen University (Grant No. 20ykzd24), and Fundamental Research Funds for the Central Universities.

Supplementary data

Supplementary data is available at PCMEDI Journal online.

Conflict of interest

None declared.

Ethics approval

The work was approved by the Ethics Committee and Animal Ethics Committee of Sun Yat-sen University Cancer Center (ethics approval number: L102012019120L; B2023-598-01).

Data availability

The miRNA sequencing data have been submitted to the NCBI Sequence Read Archive (SRA) under the accession number PRJNA1051654.

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