| Correlation of CXCL12 expression and FoxP3+ cell infiltration with human papillomavirus infection and clinicopathological progression of cervical cancer. | |
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MedLine Citation:
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PMID: 19808652 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human cervical cancer is an immunogenic tumor with a defined pattern of histopathological and clinical progression. Tumor-infiltrating T cells contribute to immune control of this tumor; however, cervical cancer dysregulates this immune response both through its association with human papillomavirus (HPV) infection and by producing cytokines and chemokines. Animal tumor models have revealed associations between overproduction of the chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) and dysregulation of tumor-specific immunity. We therefore proposed that CXCL12 expression by cervical precancerous and cancerous lesions correlates with histopathological progression, loss of immune control of the tumor, and HPV infection. We found a significant association between cancer stage and CXCL12 expression for squamous and glandular lesions as well as with the HPV16+ (high-risk) status of the neoplastic lesions. Cancer progression was correlated with increasing levels of FoxP3 T-cell infiltration in the tumor. FoxP3 and CXCL12 expression significantly correlated for squamous and glandular neoplastic lesions. These observations were supported by enzyme-linked immunosorbent assay and Western blotting. In addition, we demonstrated CXCL12 expression by dyskaryotic cells in ThinPrep cervical smears. This study robustly links increased CXCL12 expression and FoxP3(+)-cell infiltration to HPV infection and progression of cervical cancer. It supports the detection of CXCL12 in cervical smears and biopsies as an additional biomarker for this disease. |
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Authors:
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Fatimah Jaafar; Elda Righi; Victoria Lindstrom; Christine Linton; Mahrokh Nohadani; Susan Van Noorden; Tyler Lloyd; Joshua Poznansky; Gordon Stamp; Roberto Dina; Dulcie V Coleman; Mark C Poznansky |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of pathology Volume: 175 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-07 Completed Date: 2009-12-09 Revised Date: 2010-10-04 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1525-35 Citation Subset: AIM; IM |
Affiliation:
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Department of Histopathology and Cytology, Imperial College, Hammersmith Hospital, London, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkaline Phosphatase
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metabolism Antigens, CD3 / metabolism Antigens, CD4 / metabolism Antigens, CD8 / metabolism Blotting, Western Chemokine CXCL12 / metabolism* Disease Progression Enzyme-Linked Immunosorbent Assay Female Forkhead Transcription Factors / metabolism* Humans Immunohistochemistry In Situ Hybridization Lymphocytes, Tumor-Infiltrating / immunology* Papillomaviridae / physiology Papillomavirus Infections / complications*, immunology* Peroxidase / metabolism Tissue Array Analysis Uterine Cervical Neoplasms / complications, immunology, pathology*, virology* Vaginal Smears |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI49757/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD3; 0/Antigens, CD4; 0/Antigens, CD8; 0/Chemokine CXCL12; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; EC 1.11.1.7/Peroxidase; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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