The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression

Abstract

Breast cancer is a leading cause of cancer-related deaths worldwide, predominantly caused by metastasis. It is generally accepted that the pattern of breast cancer metastasis is largely determined by the interaction between the chemokine receptors on cancer cells and the chemokines expressed at the sites of metastatic disease. Chemokine receptors belong to the G-protein-coupled receptors (GPCRs) family that appear to be implicated in inflammatory diseases, tumor growth and metastasis. One of its members, C-C Chemokine receptor 7 (CCR7), binds chemokines CCL19 and CCL21, which are important for tissue homeostasis, immune surveillance and tumorigenesis. These receptors have been shown to induce the pathobiology of breast cancer due to their ability to induce cellular proliferation and migration upon the binding of the cognate chemokine receptors. The underlying signaling pathways and exact cellular interactions within this biological system are not fully understood and need further insights. Thus, in this review, we summarize the essential roles of CCR7 and its receptors in breast cancer progression. Furthermore, we discuss the mechanisms of regulation that may lead to novel opportunities for therapeutic intervention. Despite the enormous advances in our knowledge of the nature of the chemokines in breast cancer metastasis, research about the involvement of CCR7 in cancer progression is still limited. Therefore, further studies are essential to illustrate the distinct roles of CCR7 in cancer progression and validate its potential as a preventive bio-factor for human breast cancer metastasis by targeting chemokine receptor genes.

Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing

“…Moreover, CCR7 induction in EBV-infected cells was recurrently proposed to enable homing of lymphoid cells to secondary lymphoid tissue, where the virus in turn propagates infection or establishes latency, thereby driving lymphomagenesis 52 . It is further tempting to speculate on a potential role of oncogenic CCR7 mutations in EBV + DLBCL (NOS), prompting cellular proliferation and migration upon the binding of the cognate chemokine receptors, as was recently shown in breast cancer and other solid tumors 53 . Of note, we describe oncogenic mutations in DAPK1 as an exclusive feature of EBV + DLBCL (NOS).…”

CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets

“…Previous researches have proved that these signaling pathways above played key roles in tumor proliferation, migration, invasion, and metastasis. 52 , 58 And they could also affect treatment effect and clinical outcome by mediating the migration and localization of immune cells, the immune responses, and the balance between immunity and tolerance. 59–61 These data suggested that CC chemokine receptors could be used as potential immunotherapy targets.…”

CCR7 as a therapeutic target in Cancer

“…It has been postulated that cancer cells can upregulate CCR7 expression and hijack its normal functions, enabling them to migrate along the gradient of CCL19 and CCL21 towards the lymph node and colonise them as a first step towards metastasis. In support of this hypothesis, CCR7 up regulation and correlation to lymph node (LN) metastasis is demonstrated in a number of cancers including pancreatic [22], breast [23,24], oesophageal [25], head and neck [26], prostate [27,28], and colorectal [29] cancers. Moreover, the chemotactic effect of CCR7 also has been found to be involved in the migration of leukemic cells to the CNS [30].…”