Tumor-initiating cells establish an IL-33-TGF-{beta} niche signaling loop to promote cancer progression

Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation of macrophages that express the high-affinity immunoglobulin E receptor FcRIα and are in close proximity to TICs. In turn, these IL-33–responding FcRIα+ macrophages send paracrine transforming growth factor β (TGF-β) signals to TICs, inducing invasive and drug-resistant properties and further upregulating IL-33 expression. This TIC-driven, IL-33–TGF-β feedforward loop could potentially be exploited for cancer treatment.

Source: ScienceNOW - July 15, 2020 Category: Science Authors: Taniguchi, S., Elhance, A., Van Duzer, A., Kumar, S., Leitenberger, J. J., Oshimori, N. Tags: Cell Biology, Medicine, Diseases, Online Only r-articles Source Type: news