Yadav Suresh Singh, Prasad Shyam Babu, Prasad Chandra Bhushan, Pandey Lakshmi Kant, Pradhan Satyajit, Singh Sunita, Narayan Gopeshwar
Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
Department of Obstetrics and Gynecology, Banaras Hindu University, Varanasi, 221005, India.
Clin Exp Metastasis. 2016 Jun;33(5):431-9. doi: 10.1007/s10585-016-9787-9. Epub 2016 Mar 12.
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.
CXCL12是一种小的促炎趋化因子细胞因子，通过趋化因子受体CXCR4发出信号。CXCL12/CXCR4轴的重要性在与细胞存活和/或增殖以及癌症转移相关的几种不同信号通路起始信号中日益凸显。在本研究中，我们调查了CXCR4信号传导失调（由于CXCL12表达失调）是否会调节宫颈癌细胞的转移潜能。我们证明，在宫颈癌细胞系和原发性肿瘤活检中，CXCL12经常下调，其启动子高度甲基化。用重组CXCL12对外源性宫颈癌细胞系（HeLa、SiHa和C-33A）进行处理，可抑制促进转移的细胞迁移、细胞侵袭和非锚定依赖性细胞生长事件。尽管本研究需要进一步的体内验证，但我们的观察结果表明：（a）宫颈癌细胞中CXCL12的沉默可能在迁移和侵袭中起关键作用，而迁移和侵袭是癌细胞转移的关键事件；（b）CXCL12下调的宫颈癌细胞更容易被转移继发部位表达的CXCL12所吸引；（c）CXCL12通过失巢凋亡抑制非锚定依赖性细胞生长。这些发现表明CXCL12在宫颈癌中具有肿瘤抑制功能。
