D2-40/podoplanin expression in chronic villitis of the placenta

Abstract Objective.—The aim of this study was to determine the association of placental findings with cerebral palsy and related forms of neurologic impairment (NI) following birth at ≥37 weeks gestation (term). Design.—In a retrospective comparison, placentas from 40 term infants with NI ascertained on the basis of clinicopathologic review for medicolegal consultation were compared with placentas from 176 consecutive meconium-stained term infants at low risk for NI. Results.—After stratification for severity, 9 lesions were significantly increased in placentas from infants with NI: 5 lesions generally considered to occur within days of the time of labor and delivery (meconium-associated vascular necrosis, severe fetal chorioamnionitis, chorionic vessel thrombi, increased nucleated red blood cells, and findings consistent with abruptio placenta) and 4 lesions generally believed to have their onset long before labor and delivery (diffuse chronic villitis, extensive avascular villi, diffuse chorioamnionic hemosiderosis, and perivillous fibrin). Findings independently associated with NI by logistic regression in this descriptive study were severe fetal chorioamnionitis (odds ratio [OR], 13.2; 95% confidence interval [CI], 1.2–144); extensive avascular villi (OR, 9.0; 95% CI, 1.6–51); and diffuse chorioamnionic hemosiderosis (OR, 74.8; 95% CI, 6.3–894). The risk of NI increased as a function of the number of lesions present (OR, 10.1; 95% CI, 5.1–20 for each additional lesion), particularly when lesions generally considered to occur near the time of labor and those believed to occur well before labor were found in the same placenta (OR, 94.2; 95% CI, 11.9–747). Conclusions.—These findings suggest that placental pathology can contribute to an understanding of the mechanisms that contribute to NI at term.

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Podoplanin interaction with caveolin-1 promotes tumour cell migration and invasion

10.1101/488304 ◽

2018 ◽

Cited By ~ 1

Author(s):

Luisa Pedro ◽

Jacqueline D. Shields

Keyword(s):

Tumour Cell ◽

Surface Expression ◽

Alveolar Epithelial Cells ◽

Migration And Invasion ◽

Dependent Manner ◽

Caveolin 1 ◽

Alveolar Epithelial ◽

Podoplanin Expression

AbstractPodoplanin, a highly O-glycosylated type-1 transmembrane glycoprotein, found in lymphatic endothelial cells, podocytes, alveolar epithelial cells and lymph node fibroblasts is also expressed by tumour cells, and is correlated with more aggressive disease. Despite numerous studies documenting podoplanin expression, the mechanisms underlying its tumour-promoting functions remain unclear. Using a murine melanoma cell line that endogenously expresses podoplanin, we demonstrate interactions with proteins necessary for cytoskeleton reorganization, adhesion and matrix degradation, and endocytosis/receptor recycling but also identify a novel interaction with caveolin-1. We generated a panel of podoplanin and caveolin-1 variants to determine the molecular interactions and functional consequences of these interactions. Complementary in vitro and in vivo systems confirmed the existence of a functional cooperation in which surface expression of both full length, signalling competent podoplanin and caveolin-1 are necessary to induce directional migration and invasion, which is executed via PAK1 and ERK1 pathways. Our findings establish that podoplanin signalling mediates the invasive properties of melanoma cells in a caveolin-1 dependent manner.Summary StatementThis manuscript describes a new interaction and functional cooperation between podoplanin and caveolin1 that drives tumour cell invasion into surrounding tissues.

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