Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-23T09:27:21.963Z Has data issue: false hasContentIssue false
  • English
  • Français

CXC chemokine ligand 16: a Swiss army knife chemokine in cancer

Published online by Cambridge University Press:  21 April 2021

Arezoo Gowhari Shabgah ,
Maytham T. Qasim ,
Seyed Mojtaba Mostafavi ,
Angelina Olegovna Zekiy ,
Fatemeh Ezzatifar ,
Majid Ahmadi ,
Saeed Mohammadian Haftcheshmeh  and
Jamshid Gholizadeh Navashenaq Open the ORCID record for Jamshid Gholizadeh Navashenaq [Opens in a new window]
Arezoo Gowhari Shabgah
Affiliation:
School of Medicine, Bam University of Medical Sciences, Bam, Iran Student Research Committee, Bam University of Medical Sciences, Bam, Iran
Maytham T. Qasim
Affiliation:
College of Health and Medical Technology, Al-Ayen University, Thi-Qar, Iraq
Seyed Mojtaba Mostafavi
Affiliation:
HiTech Institute of Theoretical and Computational Chemistry, New Delhi, India
Angelina Olegovna Zekiy
Affiliation:
Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russia Federation
Fatemeh Ezzatifar
Affiliation:
Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
Majid Ahmadi
Affiliation:
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Saeed Mohammadian Haftcheshmeh
Affiliation:
Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
Jamshid Gholizadeh Navashenaq*
Affiliation:
Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran
*
Author for correspondence: Jamshid Gholizadeh Navashenaq, E-mail: jamshid.gholizadeh@gmail.com; jamshid.gholizadeh@mubam.ac.ir
Get access Rights & Permissions [Opens in a new window]

Abstract

Today, cancer is one of the leading causes of death worldwide. Lately, cytokine and chemokine imbalances have gained attention amongst different involved pathways in cancer development and attracted much consideration in cancer research. CXCL16, as a member of the CXC subgroup of chemokines, has been attributed to be responsible for immune cell infiltration into the tumour microenvironment. The aberrant expression of CXCL16 has been observed in various cancers. This chemokine has been shown to play a conflicting role in tumour development through inducing pro-inflammatory conditions. The infiltration of various immune and non-immune cells such as lymphocytes, cancer-associated fibroblasts and myeloid-derived suppressor cells by CXCL16 into the tumour microenvironment has complicated the tumour fate. Given this diverse role of CXCL16 in cancer, a better understanding of its function might build-up our knowledge about tumour biology. Hence, this study aimed to review the impact of CXCL16 in cancer and explored its therapeutic application. Consideration of these findings might provide opportunities to achieve novel approaches in cancer treatment and its prognosis.

Keywords

Biomarkercancercancer treatmentchemokineCXCL16CXCR6
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e4
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Griffith, JW, Sokol, CL and Luster, AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annual Review of Immunology 32, 659–702.CrossRefGoogle ScholarPubMed
Marcuzzi, E et al. (2018) Chemokines and chemokine receptors: orchestrating tumor metastasization. International Journal of Molecular Sciences 20. doi: 10.3390/ijms20010096.CrossRefGoogle ScholarPubMed
Keeley, EC, Mehrad, B and Strieter, RM (2010) CXC chemokines in cancer angiogenesis and metastases. Advances in Cancer Research 106, 91–111.CrossRefGoogle ScholarPubMed
Abel, S et al. (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-γ and TNF-α and shed by the activity of the disintegrin-like metalloproteinase ADAM10. The Journal of Immunology 172, 6362–6372.CrossRefGoogle ScholarPubMed
Shimaoka, T et al. (2000) Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. Journal of Biological Chemistry 275, 40663–40666.CrossRefGoogle ScholarPubMed
Blaak, H et al. (2005) CCR5, GPR15, and CXCR6 are major coreceptors of human immunodeficiency virus type 2 variants isolated from individuals with and without plasma viremia. Journal of Virology 79, 1686–1700.CrossRefGoogle ScholarPubMed
Matloubian, M et al. (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nature Immunology 1, 298–304.CrossRefGoogle ScholarPubMed
Hald, SM et al. (2015) Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: combined high CXCL16 expression in tumor stroma and cancer cells yields improved survival. BMC Cancer 15, 441–441.CrossRefGoogle ScholarPubMed
Abel, S et al. (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. Journal of Immunology 172, 6362–6372.CrossRefGoogle ScholarPubMed
van der Voort, R et al. (2010) An alternatively spliced CXCL16 isoform expressed by dendritic cells is a secreted chemoattractant for CXCR6+ cells. Journal of Leukocyte Biology 87, 1029–1039.CrossRefGoogle ScholarPubMed
Wang, J et al. (2008) CXCR6 induces prostate cancer progression by the AKT/mammalian target of rapamycin signaling pathway. Cancer Research 68, 10367–10376.CrossRefGoogle ScholarPubMed
Xiao, G et al. (2015) CXCL16/CXCR6 chemokine signaling mediates breast cancer progression by pERK1/2-dependent mechanisms. Oncotarget 6, 14165–14178.CrossRefGoogle ScholarPubMed
Wang, Y-H et al. (2013) Vascular endothelial cells facilitated HCC invasion and metastasis through the Akt and NF-κB pathways induced by paracrine cytokines. Journal of Experimental & Clinical Cancer Research: CR 32, 51–51.CrossRefGoogle ScholarPubMed
Liang, K et al. (2018) High CXC chemokine ligand 16 (CXCL16) expression promotes proliferation and metastasis of lung cancer via regulating the NF-κB pathway. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 24, 405–411.CrossRefGoogle ScholarPubMed
Ikeda, T et al. (2020) Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1. Cancer Science 111, 1254–1265.CrossRefGoogle ScholarPubMed
Adamski, V et al. (2017) The chemokine receptor CXCR6 evokes reverse signaling via the transmembrane chemokine CXCL16. International Journal of Molecular Sciences 18. doi: 10.3390/ijms18071468.CrossRefGoogle ScholarPubMed
Hattermann, K et al. (2016) ‘Inverse signaling’ of the transmembrane chemokine CXCL16 contributes to proliferative and anti-apoptotic effects in cultured human meningioma cells. Cell Communication and Signaling: CCS 14, 26.CrossRefGoogle Scholar
Greten, FR and Grivennikov, SI (2019) Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 51, 27–41.CrossRefGoogle ScholarPubMed
Chow, MT and Luster, AD (2014) Chemokines in cancer. Cancer Immunology Research 2, 1125–1131.CrossRefGoogle ScholarPubMed
Guo, H et al. (2019) Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA. Molecular Carcinogenesis 58, 1886–1896.CrossRefGoogle ScholarPubMed
Chalabi-Dchar, M et al. (2015) Loss of somatostatin receptor subtype 2 promotes growth of KRAS-induced pancreatic tumors in mice by activating PI3K signaling and overexpression of CXCL16. Gastroenterology 148, 1452–1465.CrossRefGoogle ScholarPubMed
Yang, H et al. (2019) Soluble CXCL16 promotes TNF-α-induced apoptosis in DLBCL via the AMAD10-NF-κB regulatory feedback loop. Cell Biology International 43, 863–874.CrossRefGoogle ScholarPubMed
Darash-Yahana, M et al. (2009) The chemokine CXCL16 and its receptor, CXCR6, as markers and promoters of inflammation-associated cancers. PLoS ONE 4, e6695.CrossRefGoogle ScholarPubMed
Ajona, D et al. (2018) Blockade of the complement C5a/C5aR1 axis impairs lung cancer bone metastasis by CXCL16-mediated effects. American Journal of Respiratory and Critical Care Medicine 197, 1164–1176.CrossRefGoogle ScholarPubMed
Zhang, F et al. (2015) MiR-451 inhibits cell growth and invasion by targeting CXCL16 and is associated with prognosis of osteosarcoma patients. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 36, 2041–2048.CrossRefGoogle ScholarPubMed
Jariwala, N et al. (2017) Oncogenic role of SND1 in development and progression of hepatocellular carcinoma. Cancer Research 77, 3306.CrossRefGoogle ScholarPubMed
Chidambaranathan-Reghupaty, S et al. (2018) The multifaceted oncogene SND1 in cancer: focus on hepatocellular carcinoma. Hepatoma Research 4, 32.CrossRefGoogle ScholarPubMed
Santhekadur, PK et al. (2012) Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor κB and miR-221*. Journal of Biological Chemistry 287, 13952–13958.CrossRefGoogle ScholarPubMed
Santhekadur, PK et al. (2012) Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor κB and miR-221. Journal of Biological Chemistry 287, 13952–13958.CrossRefGoogle ScholarPubMed
Wang, Z et al. (2020) miR-873-5p inhibits cell migration and invasion of papillary thyroid cancer via regulation of CXCL16. OncoTargets and Therapy 13, 1037–1046.CrossRefGoogle ScholarPubMed
Chaturvedi, P et al. (2014) Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment. Proceedings of the National Academy of Sciences of the USA 111, E2120–E2129.CrossRefGoogle ScholarPubMed
Yoon, MS et al. (2016) Irradiation of breast cancer cells enhances CXCL16 ligand expression and induces the migration of natural killer cells expressing the CXCR6 receptor. Cytotherapy 18, 1532–1542.CrossRefGoogle ScholarPubMed
Matsumura, S et al. (2008) Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. Journal of Immunology 181, 3099–3107.CrossRefGoogle ScholarPubMed
Ma, C et al. (2018) Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science (New York, N.Y.) 360. doi: 10.1126/science.aan5931.CrossRefGoogle ScholarPubMed
Adamski, V et al. (2020) Entry and exit of chemotherapeutically-promoted cellular dormancy in glioblastoma cells is differentially affected by the chemokines CXCL12, CXCL16, and CX3CL1. Oncogene 39, 4421–4435.CrossRefGoogle ScholarPubMed
Jung, Y et al. (2013) Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis. Nature Communications 4, 1795–1795.CrossRefGoogle ScholarPubMed
Krawczyk, KM et al. (2017) Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages. Laboratory Investigation: A Journal of Technical Methods and Pathology 97, 1296–1305.CrossRefGoogle ScholarPubMed
Takiguchi, G et al. (2016) Wnt5a-Ror2 signaling in mesenchymal stem cells promotes proliferation of gastric cancer cells by activating CXCL16-CXCR6 axis. Cancer Science 107, 290–297.CrossRefGoogle ScholarPubMed
Mir, H et al. (2019) Higher CXCL16 exodomain is associated with aggressive ovarian cancer and promotes the disease by CXCR6 activation and MMP modulation. Scientific Reports 9, 2527.CrossRefGoogle ScholarPubMed
Hu, W et al. (2008) CXCR6 is expressed in human prostate cancer in vivo and is involved in the in vitro invasion of PC3 and LNCap cells. Cancer Science 99, 1362–1369.CrossRefGoogle ScholarPubMed
Hong, L et al. (2018) Tumor-associated macrophages promote the metastasis of ovarian carcinoma cells by enhancing CXCL16/CXCR6 expression. Pathology Research and Practice 214, 1345–1351.CrossRefGoogle ScholarPubMed
Allaoui, R et al. (2016) Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers. Nature Communications 7, 13050.CrossRefGoogle ScholarPubMed
Liu, J et al. (2016) Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways. Cancer Letters 379, 49–59.CrossRefGoogle ScholarPubMed
Singh, R et al. (2016) CXCR6-CXCL16 axis promotes prostate cancer by mediating cytoskeleton rearrangement via Ezrin activation and αvβ3 integrin clustering. Oncotarget 7, 7343–7353.CrossRefGoogle ScholarPubMed
Taghizadeh, R et al. (2010) CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells. PLoS ONE 5, e15183.CrossRefGoogle ScholarPubMed
Kapur, N et al. (2019) Prostate cancer cells hyper-activate CXCR6 signaling by cleaving CXCL16 to overcome effect of docetaxel. Cancer Letters 454, 1–13.CrossRefGoogle ScholarPubMed
Han, EC et al. (2014) Tumor-conditioned Gr-1( + )CD11b( + ) myeloid cells induce angiogenesis through the synergistic action of CCL2 and CXCL16 in vitro. Biochemical and Biophysical Research Communications 443, 1218–1225.CrossRefGoogle ScholarPubMed
Cho, SW et al. (2016) CXCL16 signaling mediated macrophage effects on tumor invasion of papillary thyroid carcinoma. Endocrine-Related Cancer 23, 113–124.CrossRefGoogle ScholarPubMed
Kim, MJ et al. (2019) CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer. Scientific Reports 9, 13288.CrossRefGoogle ScholarPubMed
Fang, Y et al. (2014) Chemokine CXCL16 expression suppresses migration and invasiveness and induces apoptosis in breast cancer cells. Mediators of Inflammation 2014, 478641.CrossRefGoogle ScholarPubMed
Kee, J-Y et al. (2014) CXCL16 suppresses liver metastasis of colorectal cancer by promoting TNF-α-induced apoptosis by tumor-associated macrophages. BMC Cancer 14, 949–949.CrossRefGoogle ScholarPubMed
Cullen, R et al. (2009) Enhanced tumor metastasis in response to blockade of the chemokine receptor CXCR6 is overcome by NKT cell activation. Journal of Immunology 183, 5807–5815.CrossRefGoogle ScholarPubMed
Kee, JY et al. (2013) Chemokine CXCL16 suppresses liver metastasis of colorectal cancer via augmentation of tumor-infiltrating natural killer T cells in a murine model. Oncology Reports 29, 975–982.CrossRefGoogle ScholarPubMed
Grujic, M et al. (2017) The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung. Oncotarget 8, 25066–25079.CrossRefGoogle ScholarPubMed
Hojo, S et al. (2007) High-level expression of chemokine CXCL16 by tumor cells correlates with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer. Cancer Research 67, 4725–4731.CrossRefGoogle ScholarPubMed
Lepore, F et al. (2018) CXCL16/CXCR6 axis drives microglia/macrophages phenotype in physiological conditions and plays a crucial role in glioma. Frontiers in Immunology 9, 2750.CrossRefGoogle Scholar
Li, G et al. (2013) The transmembrane chemokines CXCL16 and CX3CL1 and their receptors are expressed in human meningiomas. Oncology Reports 29, 563–570.CrossRefGoogle ScholarPubMed
Held-Feindt, J et al. (2008) Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas. Glia 56, 764–774.CrossRefGoogle ScholarPubMed
Airoldi, I et al. (2008) CXCR5 may be involved in the attraction of human metastatic neuroblastoma cells to the bone marrow. Cancer Immunology Immunotherapy 57, 541–548.CrossRefGoogle ScholarPubMed
Ludwig, A et al. (2005) Enhanced expression and shedding of the transmembrane chemokine CXCL16 by reactive astrocytes and glioma cells. Journal of Neurochemistry 93, 1293–1303.CrossRefGoogle ScholarPubMed
Matsumura, S and Demaria, S (2010) Up-regulation of the pro-inflammatory chemokine CXCL16 is a common response of tumor cells to ionizing radiation. Radiation Research 173, 418–425.CrossRefGoogle ScholarPubMed
Huang, Y et al. (2013) Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer. Chinese Journal of Cancer 32, 289–296.CrossRefGoogle ScholarPubMed
Xing, YN et al. (2012) Role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinomas. Human Pathology 43, 2299–2307.CrossRefGoogle ScholarPubMed
Lee, HS et al. (2014) Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells. Nutrition and Cancer 66, 938–945.CrossRefGoogle ScholarPubMed
Shantha Kumara, HMC et al. (2018) Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1 month after minimally invasive colorectal cancer resection. World Journal of Surgical Oncology 16, 132.CrossRefGoogle ScholarPubMed
AbdelMageed, M et al. (2019) The chemokine CXCL16 is a new biomarker for lymph node analysis of colon cancer outcome. International Journal of Molecular Sciences 20. doi: 10.3390/ijms20225793.CrossRefGoogle ScholarPubMed
Chung, S et al. (2015) Identification of novel biomarkers for metastatic colorectal cancer using angiogenesis-antibody array and intracellular signaling array. PLoS ONE 10, e0134948.CrossRefGoogle ScholarPubMed
Zhu, Y et al. (2015) MEK inhibitor diminishes nasopharyngeal carcinoma (NPC) cell growth and NPC-induced osteoclastogenesis via modulating CCL2 and CXCL16 expressions. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 36, 8811–8818.CrossRefGoogle ScholarPubMed
Liu, F et al. (2013) CXC chemokine ligand 16, inversely correlated with CD99 expression in Hodgkin Reed-Sternberg cells, is widely expressed in diverse types of lymphomas. Oncology Reports 30, 783–792.CrossRefGoogle ScholarPubMed
Richardsen, E et al. (2015) The prognostic significance of CXCL16 and its receptor C-X-C chemokine receptor 6 in prostate cancer. American Journal of Pathology 185, 2722–2730.CrossRefGoogle ScholarPubMed
Ha, HK et al. (2011) Clinical significance of CXCL16/CXCR6 expression in patients with prostate cancer. Molecular Medicine Reports 4, 419–424.Google ScholarPubMed
Wente, MN et al. (2008) Expression and potential function of the CXC chemokine CXCL16 in pancreatic ductal adenocarcinoma. International Journal of Oncology 33, 297–308.Google ScholarPubMed
Lu, Y et al. (2008) CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro. Molecular Cancer Research 6, 546–554.CrossRefGoogle ScholarPubMed
Gooden, MJ et al. (2014) Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity. British Journal of Cancer 110, 1535–1544.CrossRefGoogle ScholarPubMed
Guo, L et al. (2011) Chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 correlate with lymph node metastasis in epithelial ovarian carcinoma. Chinese Journal of Cancer 30, 336–343.CrossRefGoogle ScholarPubMed
Chew, V et al. (2019) Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma. Gut 68, 335–346.CrossRefGoogle ScholarPubMed
Gao, Q et al. (2012) CXCR6 upregulation contributes to a proinflammatory tumor microenvironment that drives metastasis and poor patient outcomes in hepatocellular carcinoma. Cancer Research 72, 3546–3556.CrossRefGoogle ScholarPubMed
Matsushita, K et al. (2012) Soluble CXCL16 in preoperative serum is a novel prognostic marker and predicts recurrence of liver metastases in colorectal cancer patients. Annals of Surgical Oncology 19, S518–S527.CrossRefGoogle ScholarPubMed
Mir, H et al. (2015) CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases. Oncotarget 6, 9985–9998.CrossRefGoogle ScholarPubMed
Hu, W et al. (2014) CXCL16 and CXCR6 are coexpressed in human lung cancer in vivo and mediate the invasion of lung cancer cell lines in vitro. PLoS ONE 9, e99056.CrossRefGoogle ScholarPubMed
Gutwein, P et al. (2009) Tumoural CXCL16 expression is a novel prognostic marker of longer survival times in renal cell cancer patients. European Journal of Cancer 45, 478–489.CrossRefGoogle ScholarPubMed
Day, C et al. (2009) The chemokine CXCL16 is highly and constitutively expressed by human bronchial epithelial cells. Experimental Lung Research 35, 272–283.CrossRefGoogle ScholarPubMed
Shibata, Y et al. (2020) The clinical significance of CXCL16 in the treatment of advanced non-small cell lung cancer. Thoracic Cancer 11, 1258–1264.CrossRefGoogle ScholarPubMed
Farrow, NE et al. (2020) Characterization of sentinel lymph node immune signatures and implications for risk stratification for adjuvant therapy in melanoma. Annals of Surgical Oncology. doi: 10.1245/s10434-020-09277-w.CrossRefGoogle ScholarPubMed
Cassinelli, G et al. (2012) The curative efficacy of namitecan (ST1968) in preclinical models of pediatric sarcoma is associated with antiangiogenic effects. Biochemical Pharmacology 84, 163–171.CrossRefGoogle ScholarPubMed
Morris, MR et al. (2008) Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. British Journal of Cancer 98, 496–501.CrossRefGoogle ScholarPubMed
Aguirre-Ghiso, JA et al. (2003) ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Research 63, 1684–1695.Google Scholar