Potential combinatorial effects of recombinant atypical chemokine receptors in breast cancer cell invasion: A research perspective

Abstract

Abstract. Apart from their major function in the coordination of leukocyte recruitment, chemokines, in cooperation with their receptors, have been implicated in the progression of various diseases including different types of cancer, affecting survival, proliferation and metastasis. A complex network of chemokines and receptors exists in the tumor microenvironment and affects tumor development in various ways where chemokines activate typical signalling pathways by binding to the respective receptors. The identification and characterization of a group of atypical chemokine receptors [D6, Duffy antigen receptor for chemokines (DARC), ChemoCentryx chemokine receptor (CCX-CKR) and CXCR7] which appear to use unique biochemical properties to regulate the biological activities of these chemokines, is useful in the effort to therapeutically manipulate chemokines in a broad spectrum of diseases in which these chemokines play a critical role. The aim of this review was to investigate the combinatorial effect of two reported atypical chemokine receptors, D6 and DARC, on breast cancer cell invasion to understand their role and therapeutic potential in cancer treatment. In this regard, findings of the present review should be confirmed via the construction of recombinant D6 and DARC clones as well as the expression of the respective recombinant proteins using the Pichia pastoris (P. pastoris) expression system is to be performed in a future study in order to support findings of the current review.

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

“…The expression of decoy receptors is mainly restricted in placental cells and endothelial cells of lymphatic afferent vessels in skin, gut and lung. [12][13][14] THE CHEMOKINE NETWORK AT THE MATERNAL-FETAL INTERFACE After the blastocyst hatches from the zona pellucida and adheres to the endometrium during the onset of the implantation window, trophoblast cells proliferate and differentiate into cytotrophoblast and syncytiotrophoblast, resulting in the formation of anchoring chorionic villous. Highly invasive cytotrophoblasts invade into the luminal epithelium and subsequently the myometrial stroma as interstitial trophoblast, which then migrate and infiltrate the endothelium, and remodel the maternal spiral arteries.…”

Atypical chemokine receptors in cancer: friends or foes?

“…When they are expressed by cancer cells, they inhibit tumor growth through scavenging of angiogenic chemokines with concomitant inhibition of tumor vascularization (ACKR1), scavenging of inflammatory chemokines that results in inhibition of myeloid cell infiltrate (ACKR2), or scavenging of homeostatic chemokines, which inhibits tumor growth and metastasis (ACKR4). Their role as tumor suppressors is also supported by evidence from patient samples in which these 3 receptors are down-regulated by tumor cells during progression [55]. We have found that, in Kaposi sarcoma, ACKR2 is a target of the oncogenic pathway KRas/BRaf/MEK/MAPK [54]; however, it is unknown which is the mechanism of down-regulation for ACKR1 and ACKR4.…”

“…ACKR2 is expressed by breast cancer cells, and in this tumor, it has a protective role, even if it is still unclear whether normal epithelial cells express the receptor [55]. Indeed ACKR2 overexpression in a human breast cell line decreases levels of inflammatory chemokines and tumor aggressiveness; in human breast cancer samples, ACKR2 expression is inversely correlated to lymph node metastasis, as well as to clinical stage, and positively correlated to disease-free survival rate [56].…”

BioXpress: an integrated RNA-seq-derived gene expression database for pan-cancer analysis

“…Furthermore, literature evidence reveals that eight of the 9 genes in Table 2 are genes known to be associated with cancer. For example, the first gene listed in Table 2 , CCL21, participates in leukocytes and cancer cell migration through the CCR7/CCL19 (CCL21) axis to promote the growth and metastasis of various tumors such as breast cancer, melanoma, non-small cell lung cancer, head and neck, gastrointestinal and hematologic cancer ( 49 ). Second, γ-glutamyltransferase is involved in cellular glutathione homeostasis, its expression is often significantly increased in human tumors and its role in tumor progression, invasion and drug resistance has been repeatedly suggested ( 50 ).…”