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bioRxiv · 10.1101/2020.03.15.993014

Expression of Toll like Receptor 4 in the ductal epithelial cells of the Breast tumor microenvironment is correlated with the invasiveness of the tumor

MOIRANGTHEM, A.·MUKHERJEE, M.·BANDYOPADHYAY, B.·BONDHOPADHYAY, A.·MUKHERJEE, N.·KONAR, K.·Das, T.·DUTTA, P.·BASU, A.
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Abstract

Toll like receptors are expressed by variety of cells, mainly immune cells and also found to have role in the tumor microenvironment. Among them, Toll like receptors-4 is found to modulate tumor progression. But definitive action of TLR4 in tumor progression is not well understood. In the present study, in breast tumor samples, expression of TLR4 was studied by immunohistochemistry method while MMP2 and MMP9 expression were studied by gelatin zymography. Kaplan Meier plotter was used to test survivability. Breast cancer cells - MCF7, MDA MB 231, T47D were studied in the presence of TLR4 lignd LPS, with the help of MTT assay, BrdU incorporation assay, scratch wound healing assay and invasion assay. Activation of TLR4 in MCF7 which is TP53 wild type has no significant effect in proliferative rate, adhesiveness and invasiveness. While in MDA-MB-231 and T47D which are TP53 mutant, there were a significant increase in adhesiveness and migratory ability, observed., TLR4 had been expressed in breast tumor of invasive ductal carcinoma (IDC) and was found to be significantly correlated with lymph node involvement. Kaplan Meier plotter analysis revealed that high TLR4 expression might serve as an immune-protectant in invading cancer cells of TP53 wild state. It has been revealed that activation of TLR4 in breast cancer cells leads to higher expression of EMT related genes along with matrix metalloproteinases helping in migration and invasion of cells. Kaplan Meier plotter analysis revealed that TP53 wild status of the patient along with high TLR4 expression has a good overall survival of the patients.

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MOIRANGTHEM, A., MUKHERJEE, M., BANDYOPADHYAY, B., BONDHOPADHYAY, A., MUKHERJEE, N., KONAR, K., Das, T., DUTTA, P., BASU, A.. 2020-03-16. Expression of Toll like Receptor 4 in the ductal epithelial cells of the Breast tumor microenvironment is correlated with the invasiveness of the tumor. https://doi.org/10.1101/2020.03.15.993014

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