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.

Identification of Prognostic miRNA Signature and Lymph Node Metastasis-Related Key Genes in Cervical Cancer

“…Table 4 compares the expression of these seven key genes in cervical cancer, other cancers, and lymph node metastasis as reported in previous experimental studies and our calculated results. The decreased expression of CXCL12 in cervical cancer cells and its role in lymph node metastasis was confirmed in previous experiments (Yadav et al, 2016), and the decreased expression of IGF1 and the increased expression of WDHD1 were also experimentally validated in cervical cancer cells but only in lymph node metastasis of other cancers (Serrano et al, 2006;Kümmel et al, 2007;Huang et al, 2008;Zhou et al, 2016;Liu et al, 2019). Interestingly, the expression of RAD51B is also decreased in cervical cancer cells, but experiments showed that its expression is increased in other cancer lymph node metastases (Cheng et al, 2016;Hang et al, 2016).…”

“…CXCL12 is the ligand for the G-protein coupled receptor-like chemokine (C-X-C motif) receptors 4 and 7. It affects many cellular processes such as immune monitoring, inflammatory response, tumor growth, and metastasis (Colamussi et al, 2001;Yadav et al, 2016). Yadav et al (2016) demonstrated that CXCL12 expression is absent in cervical cancer.…”

Histone hypoacetylation contributes to CXCL12 downregulation in colon cancer: impact on tumor growth and cell migration

“…A recent paper indicated that in cervical cancer cells, epigenetic reactivation of CXCL12 was observed when cells are treated with both methylation-inhibiting and acetylating agents, suggesting that in cervical cancer also, methylation and histone acetylation may participate to control the CXCL12 expression level [ 26 ].…”

PBX3 is associated with proliferation and poor prognosis in patients with cervical cancer

“…The colonies were incubated for 10 days. 22 The experiment was performed three times independently for each cell line.…”