Role of tumor-derived exosomes in metastasis, drug resistance and diagnosis of clear cell renal cell carcinoma

Abstract

Renal cancer is one of the most extensively studied human tumors today, with clear cell renal cell carcinoma accounting for approximately 80% of all cases. Despite recent advances in research on clear cell renal cell carcinoma, advanced distant metastasis of the disease, delay in diagnosis, as well as drug resistance remain major problems. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, exosomes have attracted widespread attention for their role in tumor development. It has been reported that tumor-derived exosomes may act as regulators and have an important effect on the metastasis, drug resistance formation, and providing targets for early diagnosis of clear cell renal cell carcinoma. Therefore, the extensive study of tumour-derived exosomes will provide a meaningful reference for the development of the diagnostic and therapeutic field of clear cell renal cell carcinoma. This article reviews the biological role and research progress of tumor-derived exosomes in different aspects of premetastatic niche formation, tumor angiogenesis, and epithelial-mesenchymal transition during the progression of clear cell renal cell carcinoma. In addition, the role of tumor-derived exosomes in the development of drug resistance in clear cell renal cell carcinoma is also addressed in this review. Furthermore, recent studies have found that cargoes of exosomes in serum and urine, for example, a series of miRNAs, have the potential to be biological markers of clear cell renal cell carcinoma and provide meaningful targets for early diagnosis and monitoring of tumors, which is also covered in this article.

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

“…Significantly enough, another study found polymerase 1 and transcriptase release factor (PTRF) to be higher in ccRCC patients compared to healthy controls and that it diminished after nephrectomy, suggesting its involvement in the kidney TME [140]. Moreover, application of high throughput sequencing detected five novel mRNAs specific for stage I ccRCC in urinary exosomes, including NME2, AAMP, CAPNS1, VAMP8, and MYL12B [66,141]. More studies and large sample sizes are required to identify the diagnostic capacity of these EV-derived biomarkers for RCC.…”

“…EVs secreted in the TME can contribute to RCC development and progression [65]. Most EV studies have focused on ccRCC [66] (A detailed list of renal cancer derived EV markers is provided in Table 1). One study found that high levels of a lncRNA in serum (LNARSR), a type of EV cargo in plasma, can differentiate patients with ccRCC from healthy controls [67].…”

“…The formation and evolution of cancer is significantly influenced by EVs and their functional involvement in intercellular communication within the TME. Studies comparing EVs from tumor cells and EVs derived from non-tumor cells have demonstrated the important role of these entities in intercellular communication, tumor progression to metastasis, and the landscape of the TME promoting dispersion of organ-confined disease [66]. The release of tumor-secreted factor (TSF) and tumor-secreted exosome (TSE) mediates the TME to adapt to become suitable for the migration of tumor cells in secondary organs [66,150].…”

Exosomes: Diagnostic and Therapeutic Implications in Cancer

“…Exosomal proteins play important roles in various life processes [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] ( Figure 2 ). It is known that tumorigenesis is closely associated with immune evasion [ 17 ].…”

“…Exosomes mediate cell-to-cell communication [ 9 , 11 ], and exosomal contents mediate the effects of exosomes on various life processes. Exosomes are involved in angiogenesis [ 12 ], metastasis [ 13 , 14 , 15 ], anticancer drug resistance [ 16 ], immune evasion [ 17 ], macrophage polarization [ 18 ], and metabolic reprogramming [ 19 ]. Altogether, these reports suggest that exosomes may contribute to the pathogenesis of diseases.…”