Protein Tyrosine Phosphatase Receptor Zeta 1 as a Potential Target in Cancer Therapy and Diagnosis.

Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is a type V transmembrane tyrosine phosphatase that is highly expressed during embryonic development, while its expression during adulthood is limited. PTPRZ1 is highly detected in the central nervous system, affecting oligodendrocytes' survival and maturation. In gliomas, PTPRZ1 expression is significantly upregulated and is being studied as a potential cancer driver and as a target for therapy. PTPRZ1 expression is also increased in other cancer types, but there are no data on the potential functional significance of this finding. On the other hand, low PTPRZ1 expression seems to be related to a worse prognosis in some cancer types, suggesting that in some cases, it may act as a tumor-suppressor gene. These discrepancies may be due to our limited understanding of PTPRZ1 signaling and tumor microenvironments. In this review, we present evidence on the role of PTPRZ1 in angiogenesis and cancer and discuss the phenomenal differences among the different types of cancer, depending on the regulation of its tyrosine phosphatase activity or ligand binding. Clarifying the involved signaling pathways will lead to its efficient exploitation as a novel therapeutic target or as a biomarker, and the development of proper therapeutic approaches.

Prechiasmatic sulcus and optic strut: an anatomic study in dry skulls.

BACKGROUND: Although safe surgical access to the cavernous sinus is related to understanding the anatomical and ethnic variants of the prechiasmatic sulcus and the optic strut, there remains a paucity of studies of the morphology and the bony relationships in the region. The present study provides a systematic morphological and morphometric analysis of the sulcal region and the optic strut anatomy and their relations in a Greek population. METHODS: The interoptic distance, length of planum sphenoidale, sulcal length and sulcal angle was determined in 96 Greek adult dry skulls. The prechiasmatic sulci and optic struts were morphologically classified and association of sulcal region measures according to type of prechiasmatic sulcus and optic strut were examined. RESULTS: Mean interoptic distance was 1.69 ± 0.25 cm; sulcal length, 0.72 ± 0.18 cm; length of planum sphenoidale, 1.86 ± 0.32 cm; sulcal angle, 24.05 ± 17.17°. The sulcal angle was significantly smaller in female skulls compared to males (14.82 ± 12.43 vs 28.29 ± 15.24; p < 0.05). Type I (narrow, steep) prechiasmatic sulci were the most commonly observed (35.8%), followed by Type IV (wide, flat) (32.1%), Type II (narrow, flat) (18.5%) and, finally, Type III (wide, steep) sulci (13.6%). The optic strut was presulcal in 8.3% of specimens, sulcal in 31%, postsulcal in 41.7% and asymmetric in 19%. CONCLUSIONS: The present study augments the current knowledge of the morphology of key anatomical landmarks, prechiasmatic sulcus and the optic strut, for cavernous sinus surgery and indicates population and gender differences. We report significant anatomical variations in the prechiasmatic sulcus, optic strut and surrounding structures. In addition to providing a better understanding of the anatomical landmarks, necessary for the safe navigation in transcranial and endoscopic procedures, the present results also suggest that surgeons must consider population differences in determining the anatomical landmarks and navigation points in the sellar region.

Targeting the interaction of pleiotrophin and VEGFA165 with protein tyrosine phosphatase receptor zeta 1 inhibits endothelial cell activation and angiogenesis.

Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is a transmembrane tyrosine phosphatase (TP) that serves as a receptor for pleiotrophin (PTN) and vascular endothelial growth factor A 165 (VEGFA165) to regulate endothelial cell migration. In the present work, we identify a PTN peptide fragment (PTN97-110) that inhibits the interaction of PTN and VEGFA165 with PTPRZ1 but not VEGF receptor 2. This peptide abolishes the stimulatory effect of PTN and VEGFA165 on endothelial cell migration, tube formation on Matrigel, and Akt activation in vitro. It also partially inhibits VEGFA165-induced VEGF receptor 2 activation but does not affect ERK1/2 activation and cell proliferation. In vivo, PTN97-110 inhibits or dysregulates angiogenesis in the chick embryo chorioallantoic membrane and the zebrafish assays, respectively. In glioblastoma cells in vitro, PTN97-110 abolishes the stimulatory effect of VEGFA165 on cell migration and inhibits their anchorage-independent growth, suggesting that this peptide might also be exploited in glioblastoma therapy. Finally, in silico and experimental evidence indicates that PTN and VEGFA165 bind to the extracellular fibronectin type-III (FNIII) domain to stimulate cell migration. Collectively, our data highlight novel aspects of the interaction of PTN and VEGFA165 with PTPRZ1, strengthen the notion that PTPRZ1 is required for VEGFA165-induced signaling, and identify a peptide that targets this interaction and can be exploited for the design of novel anti-angiogenic and anti-glioblastoma therapeutic approaches.