PMID- 29022185 OWN - NLM STAT- MEDLINE DCOM- 20180515 LR - 20220330 IS - 1437-7772 (Electronic) IS - 1341-9625 (Linking) VI - 22 IP - 6 DP - 2017 Dec TI - Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer. PG - 991-1000 LID - 10.1007/s10147-017-1187-x [doi] AB - CXC chemokine ligand 12 (CXCL12) is an important member of the CXC subfamily of chemokines, and has been extensively studied in various human body organs and systems, both in physiological and clinical states. Ligation of CXCL12 to CXCR4 and CXCR7 as its receptors on peripheral immune cells gives rise to pleiotropic activities. CXCL12 itself is a highly effective chemoattractant which conservatively attracts lymphocytes and monocytes, whereas there exists no evidence to show attraction for neutrophils. CXCL12 regulates inflammation, neo-vascularization, metastasis, and tumor growth, phenomena which are all pivotally involved in cancer development and further metastasis. Generation and secretion of CXCL12 by stromal cells facilitate attraction of cancer cells, acting through its cognate receptor, CXCR4, which is expressed by both hematopoietic and non-hematopoietic tumor cells. CXCR4 stimulates tumor progression by different mechanisms and is required for metastatic spread to organs where CXCL12 is expressed, thereby allowing tumor cells to access cellular niches, such as the marrow, which favor tumor cell survival and proliferation. It has also been demonstrated that CXCL12 binds to another seven-transmembrane G-protein receptor or G-protein-coupled receptor, namely CXCR7. These studies indicated critical roles for CXCR4 and CXCR7 mediation of tumor metastasis in several types of cancers, suggesting their contributions as biomarkers of tumor behavior as well as potential therapeutic targets. Furthermore, CXCL12 itself has the capability to stimulate survival and growth of neoplastic cells in a paracrine fashion. CXCL12 is a supportive chemokine for tumor neovascularization via attracting endothelial cells to the tumor microenvironment. It has been suggested that elevated protein and mRNA levels of CXCL12/CXCR4/CXCR7 are associated with human bladder cancer (BC). Taken together, mounting evidence suggests a role for CXCR4, CXCR7, and their ligand CXCL12 during the genesis of BC and its further development. However, a better understanding is still required before exploring CXCL12/CXCR4/CXCR7 targeting in the clinic. FAU - Nazari, Alireza AU - Nazari A AD - Department of Surgery, School of Medicine, Rafsanjan University of Medical Science, Rafsanjan, Iran. AD - Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. FAU - Khorramdelazad, Hossein AU - Khorramdelazad H AD - Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. FAU - Hassanshahi, Gholamhossein AU - Hassanshahi G AD - Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. ghassanshahi@gmail.com. AD - Department of Immunology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. ghassanshahi@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20171011 PL - Japan TA - Int J Clin Oncol JT - International journal of clinical oncology JID - 9616295 RN - 0 (ACKR3 protein, human) RN - 0 (CXCL12 protein, human) RN - 0 (CXCR4 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (Receptors, CXCR) RN - 0 (Receptors, CXCR4) SB - IM EIN - Int J Clin Oncol. 2018 Mar 10;:. PMID: 29526013 MH - Chemokine CXCL12/chemistry/*metabolism MH - Humans MH - Molecular Targeted Therapy/methods MH - Neovascularization, Pathologic MH - Receptors, CXCR/chemistry/*metabolism MH - Receptors, CXCR4/chemistry/*metabolism MH - Signal Transduction MH - Tumor Microenvironment MH - Urinary Bladder Neoplasms/blood supply/drug therapy/*etiology/pathology OTO - NOTNLM OT - Angiogenesis OT - Bladder cancer OT - CXCL12 OT - CXCR4 OT - CXCR7 EDAT- 2017/10/13 06:00 MHDA- 2018/05/16 06:00 CRDT- 2017/10/13 06:00 PHST- 2017/04/26 00:00 [received] PHST- 2017/08/21 00:00 [accepted] PHST- 2017/10/13 06:00 [pubmed] PHST- 2018/05/16 06:00 [medline] PHST- 2017/10/13 06:00 [entrez] AID - 10.1007/s10147-017-1187-x [pii] AID - 10.1007/s10147-017-1187-x [doi] PST - ppublish SO - Int J Clin Oncol. 2017 Dec;22(6):991-1000. doi: 10.1007/s10147-017-1187-x. Epub 2017 Oct 11.