Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

BACKGROUND: Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. RESULTS: Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased "in situ transcriptomics" analysis-gene expression profiling of laser-captured TAMs to establish their activation signature in situ-we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. CONCLUSIONS: In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy

Time dependence of the surface Fermi level of GaAs in atmosphere

This letter reports the time dependence of the surface Fermi level of GaAs grown by molecular‐beam epitaxy and then exposed to atmosphere. The sheet resistance of sample structures for field effect transistors alternately increased, decreased, increased, and decreased to become nearly constant after about 500 h. These changes correspond to the surface Fermi level varying between 0.3 and 0.7 eV and finally settling 0.7 eV above the valence band maximum. Comparison between annealed and unannealed samples with low‐temperature‐grown GaAs layers showed that the pinning of the surface Fermi level at 0.7 eV above the valence band maximum is caused by arsenic antisite defects. The result supports the advanced unified defect model