Abstract
Metastasis still represents the primary cause of cancer morbidity and mortality worldwide. Chemokine signalling contributes to the overall process of cancer growth and metastasis, and their expression in both primary tumors and metastatic lesions correlate with prognosis. Chemokines promote tumor metastasization by directly supporting cancer cell survival and invasion, angiogenesis, and by indirectly shaping the pre-metastatic niches and antitumor immunity. Here, we will focus on the relevant chemokine/chemokine receptor axes that have been described to drive the metastatic process. We elaborate on their role in the regulation of tumor angiogenesis and immune cell recruitment at both the primary tumor lesions and the pre-metastatic foci. Furthermore, we also discuss the advantages and limits of current pharmacological strategies developed to target chemokine networks for cancer therapy.
Highlights
Metastasis, the dynamic process of cancer cell dissemination from the primary tumors to distant organs, still represents the primary cause of cancer morbidity and mortality [1].To metastasize, tumor cells have to leave the primary tumor site, enter the bloodstream or lymphatic system and seed to other tissues in the body
According to the “seed and soil” theory developed by Paget in 1889, in order to successfully metastasize, cancer cells have to be able to respond to attractive signals that drive them towards the pre-metastatic sites and, they should be able to survive and sprout at their destination site [3,4]
As chemokines contribute to the overall process of cancer growth and metastasis, it is conceivable that a strong correlation between chemokine receptors expression and the clinical outcome of cancer patients could be found [7]
Summary
Metastasis, the dynamic process of cancer cell dissemination from the primary tumors to distant organs, still represents the primary cause of cancer morbidity and mortality [1]. Chemokines, or chemotactic cytokines, are small chemoattractant secreted molecules regulating cell positioning and cell recruitment into tissues, playing a pivotal role in embryogenesis, tissue development and immune response Chemokines and their receptors are essential mediators of directed migration of leukocytes as well as cancer cells [6]. By promoting angiogenesis and leukocyte recruitment and activation into the pre-neoplastic niches, chemokines contribute to tumor immunity both in the primary lesions and, more importantly, at the metastatic sites [19] In this manuscript, we will focus on the role of different chemokines/chemokine receptors in regulating tumor cell dissemination, angiogenesis as well as tumor immune responses (Figure 1). The latest therapeutic strategies targeting chemokine signalling to control tumor progression will be discussed
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