Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer that is generally regarded as a genetic disease with diverse intertumor and intratumor heterogeneity. This perspective review mainly outlines the up-to-date knowledge of cancer ecology and NPC progression, and presents a number of conceptual stepping-stones. At the beginning, I explicitly advocate that the nature of NPC (cancer) is not a genetic disease but an ecological disease: a multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem. The hallmarks of cancer is proposed to act as ecological factors of population fitness. Subsequently, NPC cells are described as invasive species and its metastasis as a multidirectional ecological dispersal. The foundational ecological principles include intraspecific relationship (e.g. communication) and interspecific relationship (e.g. competition, predation, parasitism and mutualism) are interpreted to understand NPC progression. “Mulberry-fish-ponds” model can well illustrate the dynamic reciprocity of cancer ecosystem. Tumor-host interface is the ecological transition zone of cancer, and tumor buddings should be recognized as ecological islands separated from the mainland. It should be noted that tumor-host interface has a significantly molecular and functional edge effect because of its curvature and irregularity. Selection driving factors and ecological therapy including hyperthermia for NPC patients, and future perspectives in such field as “ecological pathology”, “multidimensional tumoriecology” are also discussed. I advance that “nothing in cancer evolution or ecology makes sense except in the light of the other”. The cancer ecology tree is constructed to comprehensively point out the future research direction. Taken together, the establishment of NPC ecology theory and cancer ecology tree might provide a novel conceptual framework and paradigm for our understanding of cancer complex causal process and potential preventive and therapeutic applications for patients.

A small subpopulation of cancer cells with stem cell-like features might be responsible for tumour generation, progression, and chemoresistance. Hes1 influences the maintenance of certain stem cells and progenitor cells and the digestive systems. We found upregulated Hes1 in poorly differentiated cancer samples compared with well-differentiated tumour samples, and most of the adenocarcinomas exhibited significantly higher levels of Hes1 mRNA compared with that observed in matched normal colon samples. Moreover, Hes1 expression was found to be correlated with the expression of stem cell markers in colon cancer samples, and Hes1 upregulates the expression of stemness-related genes in colon cancer cells. In addition, Hes1 enhances the self-renewal properties of the stem-like cells by increasing the sizes of CD133+ cells and SP cells and the ability of tumour sphere formation. Additionally, the Hes1-overexpressing cells formed significantly larger and higher number of colonies, as determined through the colony and the soft agar assays. More importantly, Hes1 enhances the tumourigenicity of colon cancer cell lines in nude mice and exhibits a strong tumour-formation ability at a cell density of 1 × 10³. Taken together, our data indicate that Hes1 induces stem-like cell self-renewal and increases the number of tumour-initiating cells in colon cancer.

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.

Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway

Background: The self-renewal and tumourigenicity of FoxM1 in nasopharyngeal carcinoma (NPC) remain largely unknown. In this study, we attempt to investigate the self-renewal and tumourigenicity of FoxM1 and its clinical significance in nasopharyngeal carcinoma (NPC). Methods: Several assays including cell counting Kit-8 (CCK-8) assays, colony formation, flow cytometry, immunofluorescence, tumor spheres, and mice model were used to detect the biological function of FoxM1 in NPC. The association between FoxM1 and clinical pathological features, and stem cell markers was analyzed using immunohistochemistry. Results: High expression of FoxM1 was prominently present in the T4 stages, cancer cells migrating into the stroma and vasculature. Overexpression of FoxM1 enhanced tumor proliferation, cell cycle progression, migration and stress fibers formation in vitro. In NPC tissues, FoxM1 correlated significantly with stem cells-related clinical pathological features including late clinical stage, tumor recurrence and distant metastasis. Meanwhile, FoxM1 linked closely with the expression levels of stem cell markers including Nanog, Sox2, and OCT4 in tumor samples, and also promoted the expression of these stemness-related genes in vitro. Moreover, FoxM1 conferred the self-renewal properties of cancer cells by increasing side populations (SP) cells and formed larger and more tumor spheres. Importantly, FoxM1 enhanced the ability of tumourigenicity of NPC cell lines in mice xenograft. Conclusions: We demonstrate that FoxM1 greatly induces cancer progression and cancer stem cell (CSC) features in NPC.