Expression of integrins and Toll-like receptors in cervical cancer: effect of infectious agents.
We hypothesized that development of cervical cancer is associated with alterations in the expression of innate immune receptors, i.e. integrins and TLRs, and that these alterations can be induced by infectious agents. We have studied the expression of these proteins in cervical biopsy tissues and cervical cancer-derived cell lines HeLa, CaSki, SiHa, C-33 A, and ME180. Immunohistochemistry analysis demonstrated an increase in integrin αv, β3, β4, and β6 expression in the epithelium during the development of cervical cancer. A clear trend towards higher expression of integrin β6 in cell lines harbouring human papillomavirus (HPV) genetic material, compared to HPV-negative C-33 A, was observed. To investigate whether bacterial infection can alter the expression of TLRs and integrins, we infected HeLa cells by two pathogens, Escherichia coli and Pseudomonas aeruginosa, using a common bacterium of the female genital tract, Lactobacillus reuteri, as a control. Infection with E. coli or P. aeruginosa, but not with L. reuteri, significantly altered the expression of TLR and integrins, particularly of TLR4 and integrin β6. Considering that both integrin β6 and TLR4 play important roles in tumorigenesis, our data suggest that bacterial infection may trigger cancer development in HPV-infected cervical epithelium.
Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
Jeff
J
Werner
Correne A
CA
Decarlo
Nicholas
N
Escott
Ingeborg
I
Zehbe
Marina
M
Ulanova
D052685:Alphapapillomavirus / Q000276:immunology* / Q000472:pathogenicity; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002277:Carcinoma / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D002584:Cervix Uteri / Q000473:pathology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000276:immunology* / Q000473:pathology
D039641:Integrin beta Chains; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C072170:integrin beta6