Amber Kerstetter-Fogle

Cadherin-11, a Marker of the Mesenchymal Phenotype, Regulates Glioblastoma Cell Migration and Survival In Vivo

Glioblastoma multiforme (GBM) is the most malignant and lethal form of astrocytoma. The GBM patient survival time of approximately 1 year necessitates the identification of novel molecular targets and more effective therapeutics. Cadherin-11, a calcium-dependent cell–cell adhesion molecule and mesenchymal marker, plays a role in both normal tissue development and in cancer cell migration. The functional significance of cadherin-11 in GBM has not been investigated. Here, we show that cadherin-11 is expressed in human GBM tumors and human glioma stem-like cells by immunohistochemical labeling. In addition, we show that cadherin-11 is expressed in human glioma cell lines by immunoblotting. Short hairpin RNA–mediated knockdown of cadherin-11 expression in human glioma cell lines results in decreased migration and growth factor–independent cell survival in vitro. More importantly, knockdown of cadherin-11 inhibits glioma cell survival in heterotopic and orthotopic mouse xenograft models. Together, our results show the functional significance of cadherin-11 expression in GBM and provide evidence for a novel role of cadherin-11 in promoting glioma cell survival in an in vivo environment. Thus, our studies suggest cadherin-11 is a viable molecular target for therapeutic intervention in GBM. Mol Cancer Res; 10(3); 293–304. ©2012 AACR.

Highlights from the latest articles in regenerative medicine

20, 255–264 (2014).Aging unavoidably results in progres-sive decline of muscle strength, ultimately leading to compromised quality of life for the elderly. There are no pharmacologi-cal therapies currently available to prevent muscle wasting and the economic burden is expected to only keep increasing along with projected lengthening in life expectancy. Muscle stem cells (MuSCs), also referred to as satellite stem cells, are tissue-specific stem cells dedicated to the repair of muscle tissue and a target cell-type for muscle regenerative medicine. Several reports have attributed loss of MuSC regenerative capacity to changes in the aged systemic and local muscle micro-environments and not to intrinsic defects in the aging MuSC pool. A recent report by Cosgrove and co-workers

The ratio of HLA-DR and VNN2+ expression on CD14+ myeloid derived suppressor cells can distinguish glioblastoma from radiation necrosis patients

Glioblastoma (GBM) is the most aggressive and lethal type of brain cancer with a median survival of less than two years even following aggressive treatment (Stupp et al., N Engl J Med 352:987–996, 2005). Among the many challenges in treating patients with this devastating disease is the ability to differentiate Magnetic Resonance Imaging (MRI) images that appear following radiation therapy, often termed “radiation necrosis” from true GBM recurrence. Radiation necrosis (RN) and GBM are very difficult to distinguish and currently only a brain biopsy can conclusively differentiate these pathologies. In the present study, we introduce a differential diagnostic approach using a newly identified Myeloid-Derived Suppressor Cell (MDSC) biomarker, vascular non-inflammatory molecule 2 (VNN2+), in combination with expression of traditional HLA-DR on peripheral blood CD14+ monocytes isolated from GBM and/or RN patients. We performed proof-of-principle experiments confirming the sensitivity and specificity of this approach based upon the combined expression levels of HLA-DR and VNN2 among CD14+ Mo-MDSC, which we called the DR-Vanin Index or DVI. The DVI was able to distinguish GBM from RN patients with a high degree of certainty (n = 18 and n = 6 respectively; p = 0.0004). This novel, quick and inexpensive blood-based liquid biopsy could potentially replace invasive brain biopsies in differentiating GBM from RN patients using a minimally-invasive technique.

Rapid healing and skin regeneration in the African spiny mouse.

ISSN 1746-0751 10.2217/RME.12.111