Cell-intrinsic role of MYD88 adaptor protein in murine melanoma cells

TRUCCO L.D.; ROSELLI E.; ARAYA P.; MACCIONI M.

Buenos Aires

Congreso; First International Joint Meeting between the French Society for Immunology, the Latin American Society for Immunodeficiencies, and the Argentine Society for Immunology; 2015

Myeloid differentiation primary response 88 (MyD88) functions as an adaptor molecule that links members of the pattern recognition Toll-like receptors (TLR) and IL-1R superfamily to its downstream effectors. Several reports have shown that MyD88 contributes to tumor development in different models including cancer of the skin, liver, pancreas, colon, breast and sarcoma. However, how the intrinsic MyD88-dependent signaling influences the phenotype of tumor cells is incompletely understood. In this work, we assessed the impact of MyD88 depletion on cell proliferation, cell cycle and survival of murine melanoma cells. By lentiviral delivery of shRNAs in B16 cells we generate two stable MyD88-knockdown cell lines. We performed cell viability assays and observed similar proliferation rates in both MyD88-knockdown cells when compared to the scrambled (SCR) control. Furthermore, no differences were found neither in the cell cycle distribution nor in the sensitivity to chemotherapeutic agents like doxorubicin or cisplatin between SCR and MyD88 silenced cells. These characteristics remained unchanged in spite of the presence of the TLR4 agonist LPS. Nevertheless, the ablation of MyD88 was associated with an increased expression of VEGF and HIF1-alpha transcription factor, and reduced levels of matrix metallopeptidase-9 and type I interferon IFN-beta. Moreover, the cells expressing the MyD88-shRNAs showed a dissimilar in vivo tumor growth when grafted into syngeneic mice. These data suggest that autonomous-signaling through MyD88 may exert divergent activities that influences the maintenance of tumor growth.