The small extracellular vesicle-mediated intercellular transformation of CXCR1Low to CXCR1High tumour cells promotes the progression of head and neck squamous cell carcinoma.

The heterogeneity of tumour cells enables cancers to dynamically adapt to microenvironmental stresses during progression. However, the mechanism underlying the transformation and intercellular communication between heterogeneous tumour cells has remained elusive. Here, we report a "contagion model" that mediates intercellular transformation between heterogeneous tumour cells which facilitates tumour progression. Initially identifying heterogeneous expression of CXCR1, a receptor for interleukin-8, in head and neck squamous cell carcinoma (HNSCC) tumour cells, we found that CXCR1High tumour cells had higher abilities for migration and invasion. Following interleukin-8-mediated activation, CXCR1High cells transformed CXCR1Low cells into CXCR1High cells through the secretion of small extracellular vesicles (sEVs), which increased the proportion of CXCR1High cells and facilitated tumour progression. Mechanistically, we demonstrate that sEVs derived from interleukin-8-activated CXCR1High cells contain high levels of ATP citrate lyase (ACLY), which acetylates NF-κB p65 and facilitates its nuclear translocation to transcribe CXCR1 in CXCR1Low cells. That process could be inhibited by Bempedoic acid, an FDA-approved ACLY-targeted drug. Taken together, our study reveals an sEV-mediated transformation of CXCR1Low to CXCR1High cells that promotes HNSCC progression. This provides a new paradigm to explain the dynamic changes of heterogeneous tumour cells, and identifies Bempedoic acid as a potential drug for HNSCC treatment.

Incorporating zinc ion into titanium surface promotes osteogenesis and osteointegration in implantation early phase.

The objective of this study is to further investigate the feasibility of Zinc-Titanium implant as a potential implantable material in oral application in aspects of osteoblast biocompatibility, osteogenesis and osseointegration ability. First, we used plasma immersion ion implantation and deposition (PIIID) technology to introduce Zinc ion into pure Titanium surface, then we used X-ray photoelectron spectroscopy to analyze the chemical composition of modified surface layer; next, we used in vitro studies including immunological fluorescence assay and western blotting to determine responses between MG-63 osteoblast-like cell and implant. In vivo studies adopted pig model to check the feasibility of Zn-Ti implant. Results showed that in vitro and in vivo were consistent, showing that Zn ion was successfully introduced into Ti surface by PIIID technique. The chemical and physical change on modified plant resulted in the more active expressions of mRNA and protein of Type I collagen in MG-63 cells compared with non-treated implant, and the better integration ability of bones with modified implant. We confirmed the Zn-Ti implant owns the ability in promoting osteogenesis and osteointegration in early phase of implantation and is a qualified candidate in dentistry. The overview of our study can be depicted as follows.

Chemokine/GPCR Signaling-Mediated EMT in Cancer Metastasis.

Metastasis, the chief cause of cancer-related deaths, is associated with epithelial-mesenchymal transition (EMT). In the tumor microenvironment, EMT can be triggered by chemokine/G-protein-coupled receptor (GPCR) signaling, which is closely associated with tumor progression. However, the functional links between chemokine/GPCR signaling-mediated EMT and metastasis remain unclear. Herein, we summarized the mechanisms of chemokine/GPCR signaling-mediated EMT with an insight into facilitating metastasis and clarified the role of chemokine in the local invasion, intravasation, circulation, extravasation, and colonization, respectively. Moreover, several potential pathways that might contribute to EMT based on the latest studies on GPCR signaling were proposed, including signaling mediated by G protein, ß-arrestin, intracellular, dimerization activation, and transactivation. However, there is still limited evidence to support the EMT programme functional contribution to metastasis, which keeps a key question still open whether we should target EMT programme of cancer cells. Answers to that question might help develop an anticancer strategy or guide new directions for anticancer metastasis therapy.