Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer.
Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFNγ signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFNγ in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFNγ and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFNγ (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFNγ mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFNγ axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.
Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, PR, CEP 86051-970, Brazil. marla_karine@yahoo.com.br
Marla Karine
MK
Amarante
Karen Brajão
KB
de Oliveira
Roberta Losi
RL
Guembarovski
Ana Cristina
AC
da Silva do Amaral Herrera
Alda Losi
AL
Guembarovski
Walter Jorge
WJ
Sobrinho
Julio Cesar
JC
Voltarelli
Maria Angelica Ehara
MA
Watanabe
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000235:genetics
C527276:CXCR4 protein, human; C573415:IFNG protein, human; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma