C-C motif chemokine ligand 5 and C-C chemokine receptor type 5: possible diagnostic application in breast cancer patients

Abstract

The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients’ plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I – 0.7089; stage II – 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.

The Mechanism of Scopolamine’s Effect on Migration Function of Lung Cancer Cells: A Network Pharmacology and Bioinformatics Perspective

“…Research has shown that CCR5 expression is elevated in lung cancer cells and is associated with increased tumor invasiveness and metastasis. Interaction between CCR5 and its ligands can promote cancer cell migration, invasion, and resistance to apoptosis [51][52][53]. ACE (Angiotensinconverting enzyme): ACE is an enzyme that plays a crucial role in the renin-angiotensin system, which regulates blood pressure and fuid balance.…”

Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?

“…CCR5 and its ligands, particularly CCL5 have been thought to support tumor growth either directly, by driving the migration of tumor cells to tumor sites, and mostly by recruiting MDSC and dendritic cells to the tumor site [ 96 , 97 , 98 , 99 , 100 ]. Many studies showed a clear link between CCR5 and CCR5 ligands polymorphism or differential gene signature and several cancer diseases, among them: prostate cancer, breast cancer, glioblastoma, myeloid leukemia, pancreatic adenocarcinoma, Non-Small Cell Lung Cancer (NSCLC), metastatic melanoma, metastatic colorectal cancer and others [ 98 , 99 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. Following Balistreri et al [ 129 ] that observed a very low prevalence of prostate cancer in men with CCR5 delta 32 mutations, which also confers HIV resistance, we have used mice lacking CCR5 to uncover the contribution of CCR5 to the cancer resistance and found that in these mice accumulation of MDSC at the tumor site is inadequate [ 130 ].…”

CXCL12 and CXCR4 as Potential Early Biomarkers for Luminal A and Luminal B Subtypes of Breast Cancer

“… 3 , 6 New candidates being considered as potential BC markers include matrix metalloproteinases, 7 cytokines 8 and also chemokines. 9 …”

“…3,6 New candidates being considered as potential BC markers include matrix metalloproteinases, 7 cytokines 8 and also chemokines. 9 The pathogenesis of BC is a complex process, related to the patient's age, genetic, hormonal and environmental factors. 3,4,10 Among the most recent factors associated with an increased risk of BC is chronic inflammation -associated with both cancer formation and progression.…”