One of the first lines of defence against infection is the innate immune system. This mounts a non-specific response to infectious agents including bacteria and viruses. Recognition of bacterial and viral components is accomplished by a family of receptors called Toll Like Receptors (TLRs) found on the surface of innate immune cells. TLRs can also be expressed by other cells such as cancer cells.
Previous studies have shown that activation of TLRs can affect the levels of micro RNAs (miRNAs) in cells and therefore regulate which proteins are expressed (I have mentioned the role of miRNAs in cancer in previous posts). In this present study, Galli et al. found that activation of TLR3 in prostate and breast cancer cells caused an increase in four miRNAs. These miRNAs target a class of proteins called DNA methyltransferases, resulting in the loss these proteins from the cancer cells. Without these DNA methyltransferases a protein called retinoic acid receptor beta (RARβ) is produced by the cancer cells.
In a breakthrough, the group showed that drugging tumours first with an activator of TLR3 followed by retinoic acid (an activator of RARβ), caused tumours to be smaller compared to control treated tumours. This study therefore presents promising pre-clinical data for the treatment of breast and prostate cancer with this exciting combination therapy.
Galli R, Paone A, Fabbri M, Zanesi N, Calore F, Cascione L, Acunzo M, Stoppacciaro A, Tubaro A, Lovat F, Gasparini P, Fadda P, Alder H, Volinia S, Filippini A, Ziparo E, Riccioli A, Croce CM.
Toll-like receptor 3(TLR3) activation induces microRNA-dependent reexpression of functional RARβand tumor regression.
Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9812-7. doi: 10.1073/pnas.1304610110. Epub 2013 May 28.
Chen R, Alvero AB, Silasi DA, Steffensen KD, Mor G.
Oncogene. 2008 Jan 7;27(2):225-33. doi: 10.1038/sj.onc.1210907.