Functions of chemokines in the perineural invasion of tumors (Review).

The perineural invasion (PNI) of malignant tumors is a form of tumor progression in which cancer cells encroach along nerves. PNI hinders curative resection. Residual tumor cells in or around nerves can bring about local recurrence, infiltration and metastasis. This behavior is usually associated with a poor clinical prognosis. Therefore, it is necessary to investigate novel ligand-receptor crosstalk between nerves and tumor cells that promote the process of PNI. Chemokines are regarded as one of pivotal factors involved in the process of PNI. The present review collates information provided by previous studies with regard to the role of chemokines in PNI. The study presents a definition of PNI in cancer, generalizes the biological characteristics and the expression of chemokines and their receptors in cancer types associated with PNI, and discusses the underlying molecular mechanisms of chemokines, the reciprocal interactions between chemokines and other factors in PNI, and the interconnectivity of the microenvironment and chemokines. The aim of the review is to thoroughly illustrate the molecular cues of chemokines in cancer with PNI and to identify novel antitumor targets.