PMID- 33847822 OWN - NLM STAT- MEDLINE DCOM- 20211116 LR - 20211116 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 38 IP - 5 DP - 2021 Apr 13 TI - The CXCL12/CXCR7 signalling axis promotes proliferation and metastasis in cervical cancer. PG - 58 LID - 10.1007/s12032-021-01481-2 [doi] AB - C-X-C chemokine receptor 7 (CXCR7), a novel receptor of C-X-C motif chemokine ligand 12 (CXCL12), is associated with the occurrence and metastasis of various malignant tumours. However, the role, function and underlying mechanisms of CXCR7 expression in cervical cancer remain undefined. The expression level of CXCR7 was evaluated in cervical cancer samples by immunohistochemistry and real-time PCR analyses. Western blot analysis was used to examine the expression level of CXCR7 in cervical cancer cell lines. HeLa cells were genetically silenced or pharmacologically inhibited for CXCR7 or CXCR4. Transwell and CCK-8 assays were used to examine cell migration and proliferation. The expression levels of MMP2, MMP9, TIMP-1 and TIMP-2 in HeLa cells were assessed by western blot or real-time PCR. HeLa cells silenced for CXCR7 were subcutaneously injected into nude mice to form tumours. The expression of CXCR7 in nude mice was investigated by immunohistochemical staining. Tumour volumes and weights were measured. The in vivo expression levels of MMP2, MMP9, TIMP-1 and TIMP-2 were determined by western blot analysis and real-time PCR. CXCR7 was overexpressed in cervical cancer tissues and cell lines. CXCL12 was highly expressed in cervical cancer lines. CXCR7 silencing or CCX733 treatment rather than CXCR4 silencing or AMD3100 treatment suppressed the proliferation, migration and invasion of cervical cancer cells stimulated by CXCL12. In a xenograft tumour model, CXCR7 silencing or CCX733 treatment inhibited the volumes and weights of xenograft tumours. In addition, downregulation of CXCR7 decreased the expression levels of MMP2 and MMP9 but increased the expression levels of TIMP-1 and TIMP-2 in vivo. These data support the finding that the downregulation of CXCR7 suppresses the proliferation and metastasis of cervical cancer cells. Inhibition of CXCR7 may be a potential targeted therapy for cervical cancer. FAU - Xu, Leilei AU - Xu L AUID- ORCID: 0000-0001-7045-4567 AD - Department of Gynecology, The First Hospital of Huai'an Affiliated to Nanjing Medical University, West Beijing Road, Huai'an, 223300, Jiangsu, China. leileixu@tom.com. FAU - Li, Changhua AU - Li C AD - Department of Gynecology, The First Hospital of Huai'an Affiliated to Nanjing Medical University, West Beijing Road, Huai'an, 223300, Jiangsu, China. FAU - Hua, Fu AU - Hua F AD - Department of Gynecology, The First Hospital of Huai'an Affiliated to Nanjing Medical University, West Beijing Road, Huai'an, 223300, Jiangsu, China. FAU - Liu, Xiaoping AU - Liu X AD - Department of Gynecology, The First Hospital of Huai'an Affiliated to Nanjing Medical University, West Beijing Road, Huai'an, 223300, Jiangsu, China. LA - eng PT - Journal Article DEP - 20210413 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (ACKR3 protein, human) RN - 0 (CXCL12 protein, human) RN - 0 (CXCR4 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, CXCR) RN - 0 (Receptors, CXCR4) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/drug therapy/*pathology MH - Cell Division MH - Cell Line MH - Cell Line, Tumor MH - Cervix Uteri/cytology MH - Chemokine CXCL12/*physiology MH - Epithelial Cells/metabolism MH - Female MH - Humans MH - Matrix Metalloproteinases/biosynthesis MH - Mice MH - Mice, Nude MH - Molecular Targeted Therapy MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Neoplasm Proteins/antagonists & inhibitors/*physiology MH - RNA Interference MH - RNA, Small Interfering/genetics MH - Receptors, CXCR/antagonists & inhibitors/*physiology MH - Receptors, CXCR4/antagonists & inhibitors/genetics/physiology MH - Signal Transduction/*physiology MH - Uterine Cervical Neoplasms/drug therapy/*pathology MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - CXCL12 OT - CXCR7 OT - Cervical cancer OT - Metastasis EDAT- 2021/04/14 06:00 MHDA- 2021/11/17 06:00 CRDT- 2021/04/13 12:17 PHST- 2020/12/08 00:00 [received] PHST- 2021/02/13 00:00 [accepted] PHST- 2021/04/13 12:17 [entrez] PHST- 2021/04/14 06:00 [pubmed] PHST- 2021/11/17 06:00 [medline] AID - 10.1007/s12032-021-01481-2 [pii] AID - 10.1007/s12032-021-01481-2 [doi] PST - epublish SO - Med Oncol. 2021 Apr 13;38(5):58. doi: 10.1007/s12032-021-01481-2.