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

Hao-Jun Xie; Ming-Jie Jiang; Ke Jiang; Lin-Quan Tang; Qiu-Yan Chen; An-Kui Yang; Hai-Qiang Mai

doi:10.1093/pcmedi/pbae018

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

Precis Clin Med. 2024 Sep 23;7(3):pbae018. doi: 10.1093/pcmedi/pbae018. eCollection 2024 Sep.

Authors

Hao-Jun Xie^{1

2}, Ming-Jie Jiang^{1

2}, Ke Jiang^{1

2}, Lin-Quan Tang^{3

2}, Qiu-Yan Chen^{3

2}, An-Kui Yang^{1

2}, Hai-Qiang Mai^{3

2}

Affiliations

¹ Department of Head and Neck, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
² State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
³ Departcment of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

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 communication; cell heterogeneity; exosomes; metastasis; nasopharyngeal carcinoma.