Isogenic human mammary epithelial cell lines: novel tools for target identification and validation. Comprehensive characterization of an isogenic human mammary epithelial cell model provides evidence for epithelial-mesenchymal transition.

Tumorigenesis is a multi-step process involving several consecutive genetic alterations resulting in loss of genomic stability and deregulated signal transduction pathways. To study these deregulated processes in vitro, typically established cancer cell lines derived from primary tumors, ascites, or from metastases are used. However, these cancer cell lines reflect only late stages of the tumorigenic process.

RNA interference targeting protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta suppresses glioblastoma growth in vitro and in vivo.

The protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) and its ligand pleiotrophin (PTN) are overexpressed in human glioblastomas. Both molecules are involved in neuronal cell migration during CNS development. In addition, PTN can induce glioma cell migration which is at least in part mediated through binding to PTPzeta/RPTPbeta.

Contactin is expressed in human astrocytic gliomas and mediates repulsive effects.

Contactin is a cell surface adhesion molecule that is normally expressed by neurons and oligodendrocytes. Particularly high levels of contactin are present during brain development. Using subtractive cloning, we identified contactin transcripts as overexpressed in glioblastomas compared with normal brain.

Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas.

Using subtractive cloning combined with cDNA array analysis, we previously identified the genes encoding for the protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) and its ligand pleiotrophin (PTN) as overexpressed in human glioblastomas compared to normal brain. Both molecules have been implicated in neuronal migration during central nervous system development, and PTN is known to be involved in tumor growth and angiogenesis. We confirm overexpression of both molecules at the protein level in astrocytic gliomas of different malignancy grades.

A role for receptor tyrosine phosphatase zeta in glioma cell migration.

Glioblastomas (GBM) are the most frequent and malignant human brain tumor type. Typically striking in adulthood, tumor progression is rapid, relentless, and ultimately leads to the patient's death within a year of diagnosis. The identification of transcriptionally regulated genes can lead to the discovery of targets for antibody or small-molecule-mediated therapy, as well as diagnostic markers.

Glioblastoma and cerebral microvascular endothelial cell migration in response to tumor-associated growth factors.

Objective: Glioma cell migration is determined by a complex interplay between soluble motogens and extracellular matrix components. Several growth factors are thought to be involved in glioma cell migration; however, little is known about their motogenic potency relative to one another.

Methods: Using modified Boyden chamber assays, we compared the chemotactic effects of scatter factor/hepatocyte growth factor (SF/HGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, epidermal growth factor (EGF), fibroblast growth factor (FGF)-1, FGF-2, insulin-like growth factor (IGF)-1, IGF-2, platelet-derived growth factor (PDGF)-AA, PDGF-BB, vascular endothelial growth factor (VEGF), pleiotrophin (PTN), and midkine (MK) in concentrations ranging from 1 pmol/L to 50 nmol/L on three different human glioblastoma cell lines.

Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF-A.

Purpose: Vascular endothelial growth factor (VEGF)-A isa key mediator of angiogenesis in malignant gliomas. Soluble VEGF receptor 1 (sVEGFR-1) can complex VEGF-A and reduce its bioavailability. In several animal models sVEGFR-1 inhibited angiogenesis and tumor growth.