title: CXCL12 is a key regulator in tumor microenvironment of cervical cancer: an in vitro study.
abstract: CXCL12 is a small pro-inflammatory chemo-attractant cytokine which signals through chemokine receptor CXCR4. The importance of CXCL12/CXCR4 axis is coming to the fore in several divergent signaling pathway-initiating signals related to cell survival and/or proliferation and cancer metastasis. In the present study we have investigated whether deregulation in CXCR4 signaling (as a consequence of deregulated expression of CXCL12) modulate the metastatic potential of cervical carcinoma cells. We demonstrate that CXCL12 is frequently down regulated and its promoter is hypermethylated in cervical cancer cell lines and primary tumor biopsies. Exogenous treatment of cervical cancer cell lines (HeLa, SiHa and C-33A) with recombinant CXCL12 inhibited the metastasis promoting cell migration, cell invasion and anchorage independent cell growth events. Although this study will need further in vivo validation, our observations suggest that (a) silencing of CXCL12 in cervical cancer cells may be critical in migration and invasion, the key events in cancer cell metastases; (b) cervical cancer cells having down regulated CXCL12 are more prone to being attracted to CXCL12 expressed at secondary sites of metastases; and (c) CXCL12 inhibits anchorage independent cell growth via anoikis. These findings suggest the tumor suppressor functions of CXCL12 in cervical cancer.
authors.affiliation: Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Suresh Singh
authors.initials: SS
authors.lastname: Yadav
authors.affiliation: Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Shyam Babu
authors.initials: SB
authors.lastname: Prasad
authors.affiliation: Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Prasad
authors.affiliation: Department of Obstetrics and Gynecology, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Lakshmi Kant
authors.initials: LK
authors.lastname: Pandey
authors.affiliation: Department of Radiotherapy & Radiation Medicine, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Pradhan
authors.affiliation: Department of Zoology, MahilaMahavidyalaya, Banaras Hindu University, Varanasi, 221005, India. sunitas@bhu.ac.in.
authors.forename: Sunita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India. gnarayan@bhu.ac.in.
authors.forename: Gopeshwar
authors.initials: G
authors.lastname: Narayan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: Anchorage independent cell growth; CXCL12; Cell invasion; Cell migration; Cervical cancer; Promoter hypermethylation