Using an in-vivo syngeneic spontaneous metastasis model identifies ID2 as a promoter of breast cancer colonisation in the brain.

Background: Dissemination of breast cancers to the brain is associated with poor patient outcome and limited therapeutic options. In this study we sought to identify novel regulators of brain metastasis by profiling mouse mammary carcinoma cells spontaneously metastasising from the primary tumour in an immunocompetent syngeneic host.

Methods: 4T1 mouse mammary carcinoma sublines derived from primary tumours and spontaneous brain and lung metastases in BALB/c mice were subject to genome-wide expression profiling.

The embryonic type of SPP1 transcriptional regulation is re-activated in glioblastoma.

Osteopontin (SPP1, a secreted phosphoprotein 1) is primarily involved in immune responses, tissue remodelling and biomineralization. However, it is also overexpressed in many cancers and regulates tumour progression by increasing migration, invasion and cancer stem cell self-renewal. Mechanisms of SPP1 overexpression in gliomas are poorly understood.

Endosialin-Expressing Pericytes Promote Metastatic Dissemination.

Metastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts share a number of traits, including the upregulated expression of the transmembrane receptor endosialin (CD248). Comparative experiments in wild-type and endosialin-deficient mice revealed that stromal endosialin does not affect primary tumor growth but strongly promotes spontaneous metastasis.

Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response.

Gliomas attract brain-resident (microglia) and peripheral macrophages and reprogram these cells into immunosuppressive, pro-invasive cells. M-CSF (macrophage colony-stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM-CSF (granulocyte-macrophage colony-stimulating factor encoded by the CSF2 gene) but not M-CSF when compared to normal astrocytes.

TGF beta signaling and its role in glioma pathogenesis.

Transforming growth factor beta (TGF-β) signaling is involved in the regulation of proliferation, differentiation and survival/or apoptosis of many cells, including glioma cells. TGF-β acts via specific receptors activating multiple intracellular pathways resulting in phosphorylation of receptor-regulated Smad2/3 proteins that associate with the common mediator, Smad4. Such complex translocates to the nucleus, binds to DNA and regulates transcription of many genes.

Downregulation of Akt and FAK phosphorylation reduces invasion of glioblastoma cells by impairment of MT1-MMP shuttling to lamellipodia and downregulates MMPs expression.

Human malignant glioblastomas are highly invasive tumors. Increased cell motility and degradation of the surrounding extracellular matrix are essential for tumor invasion. PI3K/Akt signaling pathway emerges as a common pathway regulating cellular proliferation, migration and invasion; however, its contribution to particular process and downstream cascades remain poorly defined.