Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis.
BACKGROUND
Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.


METHODS
The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.


RESULTS
Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.


CONCLUSIONS
The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.
Unidad de Investigación, Fundación Hospital de Jove, Gijón, Spain. investigacion@hospitaldejove.com
Salomé
S
González-Reyes
Laura
L
Marín
Lucía
L
González
Luis O
LO
González
José M
JM
del Casar
Maria L
ML
Lamelas
José M
JM
González-Quintana
Francisco J
FJ
Vizoso
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D016009:Chi-Square Distribution; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain; D016019:Survival Analysis; D013997:Time Factors; D046888:Tissue Array Analysis; D051196:Toll-Like Receptor 3 / Q000032:analysis* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000032:analysis* / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000032:analysis* / Q000235:genetics; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9