Anti-lung cancer properties of cyanobacterial bioactive compounds.

Lung cancer, the most prevalent gender-independent tumor entity in both men and women, is among the leading cause of cancer-related deaths worldwide. Despite decades of effort in developing improved therapeutic strategies including immunotherapies and novel chemotherapeutic agents, only modest improvements in outcome and long-term survival of lung cancer patients have been achieved. Therefore, exploring new and exceptional sources for bioactive compounds that might serve as anti-cancer agents might be the key to improving lung cancer therapy.

Analysis of Hypoxia and the Hypoxic Response in Tumor Xenografts.

Solid tumors are often characterized by insufficient oxygen supply (hypoxia), as a result of inadequate vascularization, which cannot keep up with the rapid growth rate of the tumor. Tumor hypoxia is a negative prognostic and predictive factor and is associated with a more aggressive phenotype in various tumor entities. Activation of the hypoxic response in tumors, which is centered around the hypoxia-inducible transcription factors (HIFs), has been causally linked to neovascularization, increased radio- and chemoresistance, altered cell metabolism, genomic instability, increased metastatic potential, and tumor stem cell characteristics.

Acidosis Acts through HSP90 in a PHD/VHL-Independent Manner to Promote HIF Function and Stem Cell Maintenance in Glioma.

Hypoxia is a common feature of solid tumors, which controls multiple aspects of cancer progression. One important function of hypoxia and the hypoxia-inducible factors (HIF) is the maintenance of cancer stem-like cells (CSC), a population of tumor cells that possess stem cell-like properties and drives tumor growth. Among the changes promoted by hypoxia is a metabolic shift resulting in acidification of the tumor microenvironment.

Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR.

Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR.

PHD3 regulates EGFR internalization and signalling in tumours.

Tumours exploit their hypoxic microenvironment to induce a more aggressive phenotype, while curtailing the growth-inhibitory effects of hypoxia through mechanisms that are poorly understood. The prolyl hydroxylase PHD3 is regulated by hypoxia and plays an important role in tumour progression. Here we identify PHD3 as a central regulator of epidermal growth factor receptor (EGFR) activity through the control of EGFR internalization to restrain tumour growth.

Isolation and culture of primary glioblastoma cells from human tumor specimens.

Cultured tumor cells are a central tool in cancer research and have provided fundamental insights in tumor biology. Recent evidence, however, indicates that classically established cell lines from different tumors, including glioblastoma, do not fully reflect the genotypes and phenotypes of the respective primary tumors. By contrast, primary cells, isolated from human tumor samples and maintained in serum-free spheroid cultures at low passage under defined growth factor conditions, reproduce key aspects of tumor cell physiology much more faithfully.

Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression.

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood-brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium.

Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis.

The formation and guidance of specialized endothelial tip cells is essential for both developmental and pathological angiogenesis. Notch-1 signalling regulates the generation of tip cells, which respond to gradients of vascular endothelial growth factor (VEGF-A). The molecular cues and signalling pathways that control the guidance of tip cells are poorly understood.

A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha.

Glioma growth and progression depend on a specialized subpopulation of tumour cells, termed tumour stem cells. Thus, tumour stem cells represent a critical therapeutic target, but the molecular mechanisms that regulate them are poorly understood. Hypoxia plays a key role in tumour progression and in this study we provide evidence that the hypoxic tumour microenvironment also controls tumour stem cells.