Activation of the epidermal growth factor receptors EGFR (ErbB1) and HER2 (ErbB2) drive the progression of multiple cancer types through complex mechanisms that are still not fully understood. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. An examination of HER2 and NF-κB receptor (RANK) coexpression revealed increased levels of both proteins in aggressive prostate tumors and metastatic deposits. Inhibiting HER2 expression in bone tumor xenografts reduced proliferation and RANK expression while maintaining EGFR expression. In examining the role of EGFR in tumor-initiating cells (TIC), we found that EGFR expression was required for primary and secondary sphere formation of prostate cancer cells. EGFR expression was also observed in circulating tumor cells (CTC) during prostate cancer metastasis. Dual inhibition of HER2 and EGFR resulted in significant inhibition of tumor xenograft growth, further supporting the significance of these receptors in prostate cancer progression. Overall, our results indicate that EGFR promotes survival of prostate TIC and CTC that metastasize to bone, whereas HER2 supports the growth of prostate cancer cells once they are established at metastatic sites.
The invasion of bladder cancer into the sub-urothelial muscle and vasculature are key determinants leading to lethal metastatic progression. However, the molecular basis is poorly understood, partly because of the lack of uncomplicated and reliable models that recapitulate the biology of locally invasive disease. We developed a surgical grafting technique, characterized by a simple, rapid, reproducible and high-efficiency approach, to recapitulate the pathobiological events of human bladder cancer invasion in mice. This technique consists of a small laparotomy and direct implantation of human cancer cells into the bladder lumen. Unlike other protocols, it does not require debriding of the urothelial lining, injection into the bladder wall, specialized imaging equipment, bladder catheterization or costly surgical equipment. With minimal practice, the procedure can be executed in <10 min. Tumors develop with a high take rate, and most cell lines exhibit local invasion within 4 weeks of implantation.
The eXtendable Solar Array System (XSAS) is a CubeSat power generation and distribution system under development by a team of students at the University of Michigan. Low power generation is a major factor limiting current CubeSat capabilities. XSAS is being designed as a 1U (10 cm × 10 cm × 10 cm) CubeSat attachment capable of high power generation by utilizing an extending array of solar panels that provide a large surface compared to the common 3U (10 cm × 10 cm × 30 cm) CubeSat. The geometry of extendable structure can provide additional benefits to a mission such as passive gravity gradient stabilization and the potential to integrate with a high gain antenna for enhanced communication capabilities. Preliminary calculations on the baseline design show that XSAS provides more than 20 watt-hours average power at 100° inclination orbits above 600 km, nearly triple the average 7 watt-hours power generation capability of a 3U CubeSat. A scaled down version of the extending array was tested in microgravity and validated as a reliable design. Currently, the XSAS project is in a research and development stage. All aspects of the XSAS technology are being investigated or redesigned based on previous testing results, lessons learned, and trade studies. Modeling is being done to determine power generation capabilities with respect to a range of orbital altitude and inclinations, structural characteristics, and thermal management methods. The extending structure and electrical power system are being designed and prototyped. The group will continue to raise the Technology Readiness Level and one day utilize XSAS to benefit a CubeSat mission. L
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