Thymus antibody-secreting cells: once forgotten but not lost.

Antibody-secreting cells are essential contributors to the humoral response. This is due to multiple factors which include: 1) the ability to secrete thousands of antibodies per second, 2) the ability to regulate the immune response and 3) the potential to be long-lived. Not surprisingly, these cells can be found in numerous sites within the body which include organs that directly interface with potential pathogens (e.g., gut) and others that provide long-term survival niches (e.g., bone marrow). Even though antibody-secreting cells were first identified in the thymus of both humans and rodents in the 1960s, if not earlier, only recently has this population begun to be extensively investigated. In this article, we provide an update regarding the current breath of knowledge pertaining to thymus antibody-secreting cells and discuss the potential roles of these cells and their impact on health.

EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment.

PURPOSE: There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology. EXPERIMENTAL DESIGN: Real-time qRT-PCR was used to quantify EFEMP1 expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both in vitro and in vivo (subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems). RESULTS: Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity. CONCLUSIONS: Overall, our data reveals that EEFEMP1 suppresses glioma growth in vivo, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.