Exosomal proteins: Key players mediating pre-metastatic niche formation and clinical implications (Review)

Tumor metastasis is a destructive characteristic of malignant tumors and the fundamental reason why malignant tumors are difficult to cure. The concept of a pre-metastatic niche (PMN) provides a novel way to elucidate the molecular mechanism of tumor metastasis. At present, the PMN has been considered as a critical determinant priming distal sites for metastasis. Accumulating evidence has suggested that exosomes are cellular communicators serving a pivotal role in mediating tumor cell metastasis by establishing the PMN. Among exosomal cargos, non-coding RNAs and proteins are two commonly studied components; however, the latter has received less attention. The present review aimed to summarize the findings regarding cargo proteins selectively loaded in malignant tumor-derived exosomes. Metastasis-associated proteins have been demonstrated to be selectively enriched in malignant tumor-derived exosomes. Exosomal proteins promote PMN formation to mediate the site-specific metastasis of tumor cells by inducing lymphangiogenesis, angiogenesis and permeability, educating stromal cells, remodeling the extracellular matrix, and suppressing the antitumor immune response. These exosomal proteins have great potential in predicting organ-directed metastasis and prognosis, as well as in cancer therapy.