Abstract

CXCR7 is involved in tumor development and metastasis in multiple malignancies. However, the function and molecular mechanisms of action of CXCR7 in human cervical cancer are still unclear. In the present study a loss of-function approach was used to observe the effects of recombinant CXCR7 specific small interfering RNA pBSilence1.1 plasmids on biological behavior including proliferative activity and invasive potential, as indicated by MTT assays with the cervical cancer SiHa cell line in vitro. Reverse transcription polymerase chain reaction and Western blotting revealed that CXCR7 was downregulated in transfected compared with control cells, associated with inhibited cell growth, invasiveness and migration. The expression of CXCR7 and CXCL12 was also determined immunohistochemically in 152 paraffin-embedded, cervical squamous cell carcinoma (CSCC) and cervical intraepithelial neoplasia (CIN), or normal cervical epithelial to assess clinico-pathological pattern and CXCR7 status with respect to cell differentiation and lymph node metastasis in Uighur patients with CSCC. CXCR7 and CXCL12 expression was higher in cervical cancer than CIN and normal cervical mucosa, especially in those with higher stage and lymph node metastasis. CXCL12 appeared to be positively regulated by CXCR7 at the post-transcriptional level in CSCC. We propose that aberrant expression of CXCR7 plays a role in carcinogenesis, differentiation and metastasis of CSCC, implying its use as a potential target for clinical biomarkers in differentiation and lymph node metastasis.

Highlights

  • Advanced cervical carcinoma (CC) is one of the most commonly diagnosed cancers in women, especially in developing countries, and it is still remains a major problem in oncology due to treatment failure and distant metastasis

  • CXCR7 and CXCL12 expression was higher in cervical cancer than cervical intraepithelial neoplasia (CIN) and normal cervical mucosa, especially in those with higher stage and lymph node metastasis

  • We propose that aberrant expression of CXCR7 plays a role in carcinogenesis, differentiation and metastasis of cervical squamous cell carcinoma (CSCC), implying its use as a potential target for clinical biomarkers in differentiation and lymph node metastasis

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Summary

Introduction

Advanced cervical carcinoma (CC) is one of the most commonly diagnosed cancers in women, especially in developing countries, and it is still remains a major problem in oncology due to treatment failure and distant metastasis. The expression of the progression genes in the primary tumors has a more complex basis These metastasis-prone genes support primary tumor growth through one particular effect, whereas they enhance distant metastasis through another effect chemokines were recognized originally for their ability to dictate the migration and activation of leukocytes. Previous reports have shown that cancer cells implicate chemokines and their corresponding receptors to stimulate their own growth, invasion, and metastasis. While no data are available about the function and prognostic impact of CXCR7 in CC It is still unclear whether the CXCR7 is able to activate on the biological characteristics of the cervix cancer, such as proliferation, invasion, and migration. We investigate the expression of CXCR7 in a large number of in Uyghur CC specimens and to evaluate its potential role as a prognostic target molecule

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