The tyrosine kinase c-Met promotes the formation and malignant progression of multiple cancers. It is well known that c-Met hyperactivation increases tumorigenicity and tumor cell resistance to DNA damaging agents, properties associated with tumor-initiating stem cells. However, a link between c-Met signaling and the formation and/or maintenance of neoplastic stem cells has not been previously identified. Here, we show that c-Met is activated and functional in glioblastoma (GBM) neurospheres enriched for glioblastoma tumor-initiating stem cells and that c-Met expression/function correlates with stem cell marker expression and the neoplastic stem cell phenotype in glioblastoma neurospheres and clinical glioblastoma specimens. c-Met activation was found to induce the expression of reprogramming transcription factors (RFs) known to support embryonic stem cells and induce differentiated cells to form pluripotent stem (iPS) cells, and c-Met activation counteracted the effects of forced differentiation in glioblastoma neurospheres. Expression of the reprogramming transcription factor Nanog by glioblastoma cells is shown to mediate the ability of c-Met to induce the stem cell characteristics of neurosphere formation and neurosphere cell self-renewal. These findings show that c-Met enhances the population of glioblastoma stem cells (GBM SCs) via a mechanism requiring Nanog and potentially other c-Met–responsive reprogramming transcription factors.

Background: Coronavirus disease 2019 (COVID-19) is a syndrome that has been associated with multiple cardiac complications including myopericarditis. The pathophysiology and treatment for myopericarditis in the setting of COVID-19 infection is still under investigation. Case summary: We present a case of a 60-year-old male admitted for dyspnoea due to COVID-19. He developed new ST-segment elevation, elevated cardiac enzymes, severe left ventricular dysfunction, and high inflammatory markers in the setting of haemodynamic and respiratory collapse from the viral illness. He was diagnosed with COVID-19-induced myopericarditis. He showed rapid clinical improvement with a rapid wean off pressure support, resolution of electrocardiogram (ECG) findings, and recovery of left ventricular systolic function following treatment with intravenous immunoglobulin (IVIG) and methylprednisolone. Discussion: COVID-19’s complex and devastating complications continue to create new challenges for clinicians. Cardiac complications, specifically, have been shown to be a signal for worse prognosis in these patients. IVIG and steroids can inhibit the inflammatory cascade and decrease myocardial injury, with implications in treatment of severe myopericarditis.