The role of TLR4 in breast cancer

Wed, 06/15/2016 - 11:40

Toll like receptors (TLRs) are highly conserved proteins that are first known for their role in pathogen recognition and immune response activation.  In order to elicit the necessary immune response in reaction to a foreign pathogen, TLRs trigger cytokine production depending on the behavior patterns of the pathogen itself.  Specifically, TLR4 acts through bacterial lipopolysaccharide (LPS), which composes the outer wall of Gram-negative bacteria.  Bacterial LPS is also a potent activator of the immune system.  Essentially, LPS is a ligand to TLR4, which in turn interacts with myeloid differentiation protein 2 (MD-2), CD14 and LPS-binding protein (LBP), which exist in the extracellular space.  This interaction turns on a signaling cascade that leads to the production of the required cytokines to trigger an effective immune response. 

TLR4 antibody

TLR4 Antibody (76B357.1) [NB100-56566] - IHC-P analysis of Rat's salivary gland tissue section (NBP2-30228) using TLR4 antibody (clone 76B357.1) at 1:100 dilution. The antibody generated a membrane-cytoplasmic staining in the tissue with stronger signal in ductal epithelial cells.

While the role of TLR4 in innate immune response is well established, recent research aims to elucidate the role of TLR4 in breast cancer.  Haricharan et al found that TLR4 drives breast cancer cell growth based on the presence of the tumor suppressor protein p53.  Their group used primary antibodies, including a TLR antibody, alongside an R&D Systems cytokine array kit, to measure the activity of various proteins during this immune response.   Their results suggested that TLR4 activation inhibits the growth of resident p53, yet promoted the growth of mutant p53.   In this case, Haricharan et al discovered that this is achieved through induction of ILN-gamma and subsequent activation of p21. These findings contradict previous research that shows TLR4 acting as a tumor promoter. 

Similarly, Mehmeti et al looked into the expression of TLR4 and co-receptor expression in breast cancer.  Overall, TLR4 expression patterns were observed through RT-qPCR and immunohistochemistry (IHC) using TLR4 antibodies on estrogen receptor positive, and estrogen receptor positive/progesterone receptive negative, breast cancer cell lines.  Overall, they found that TLR4 is primarily expressed in estrogen receptor/progesterone receptor negative breast cancers, and that TLR4 is a potential therapeutic target in this type of cancer by decreasing the pro-inflammatory microenvironment.  Rajput et al used a TLR4 Antibody to further investigate the role of TLR4 and its ability to serve as a determinant of breast cancers response to the clinical drug paclitaxel.  In a bacterial environment, LPS is the activator of the TLR4 response; however, bacterial LPS is an unlikely component of human breast cancers.  They found that paclitaxel activated TLR4 shows promise when chemoresistance begins by increasing the anti-inflammatory response of the cells being targeted. 

Novus Biologicals offers TLR4 reagents for your research needs including:

  1. PMID: 26392082
  2. PMID: 26063617
  3. PMID: 23720768

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