uPARAP/Endo180: a multifaceted protein of mesenchymal cells.

peer reviewedThe urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180) is already known to be a key collagen receptor involved in collagen internalization and degradation in mesenchymal cells and some macrophages. It is one of the four members of the mannose receptor family along with a macrophage mannose receptor (MMR), a phospholipase lipase receptor (PLA2R), and a dendritic receptor (DEC-205). As a clathrin-dependent endocytic receptor for collagen or large collagen fragments as well as through its association with urokinase (uPA) and its receptor (uPAR), uPARAP/Endo180 takes part in extracellular matrix (ECM) remodeling, cell chemotaxis and migration under physiological (tissue homeostasis and repair) and pathological (fibrosis, cancer) conditions. Recent advances that have shown an expanded contribution of this multifunctional protein across a broader range of biological processes, including vascular biology and innate immunity, are summarized in this paper. It has previously been demonstrated that uPARAP/Endo180 assists in lymphangiogenesis through its capacity to regulate the heterodimerization of vascular endothelial growth factor receptors (VEGFR-2 and VEGFR-3). Moreover, recent findings have demonstrated that it is also involved in the clearance of collectins and the regulation of the immune system, something which is currently being studied as a biomarker and a therapeutic target in a number of cancers

The pre‐metastatic niche in lymph nodes: formation and characteristics

peer reviewe

Periostin in lymph node pre-metastatic niches governs lymphatic endothelial cell functions and metastatic colonization.

peer reviewedAlthough lymph node (LN) metastasis is an important prognostic parameter in cervical cancer, the tissue remodeling at a pre-metastatic state is poorly documented in LNs. We here identified periostin (POSTN) as a component of non-metastatic LNs by applying proteomic analyses and computerized image quantifications on LNs of patients with cervical cancer. We provide evidence for remarkable modifications of POSTN and lymphatic vessel distributions and densities in non-metastatic sentinel and metastatic human LNs, when compared to distant non-metastatic LNs. POSTN deposition at a pre-metastatic stage was demonstrated in a pre-clinical murine model (the ear sponge assay). Its expression by fibroblastic LN cells was assessed by in situ hybridization and in vitro cultures. In vitro, POSTN promoted lymphatic endothelial cell functions and tumor cell proliferation. Accordingly, the in vivo injection of recombinant POSTN together with VEGF-C boosted the lymphangiogenic response, while the metastatic potential of tumor cells was drastically reduced using a POSTN blocking antibody. This translational study also supports the existence of an unprecedented dialog "in cascade", between the primary tumor and the first pelvic nodal relay in early cervical cancer, and subsequently from pelvic LN to para-aortic LNs in locally advanced cervical cancers. Collectively, this work highlights the association of POSTN deposition with lymphangiogenesis in LNs, and provides evidence for a key contribution of POSTN in promoting VEGF-C driven lymphangiogenesis and the seeding of metastatic cells

Improved SOT (Hinode mission) high resolution solar imaging observations

We consider the best today available observations of the Sun free of turbulent Earth atmospheric effects, taken with the Solar Optical Telescope (SOT) onboard the Hinode spacecraft. Both the instrumental smearing and the observed stray light are analyzed in order to improve the resolution. The Point Spread Function (PSF) corresponding to the blue continuum Broadband Filter Imager (BFI) near 450 nm is deduced by analyzing i/ the limb of the Sun and ii/ images taken during the transit of the planet Venus in 2012. A combination of Gaussian and Lorentzian functions is selected to construct a PSF in order to remove both smearing due to the instrumental diffraction effects (PSF core) and the large-angle stray light due to the spiders and central obscuration (wings of the PSF) that are responsible for the parasitic stray light. A Max-likelihood deconvolution procedure based on an optimum number of iterations is discussed. It is applied to several solar field images, including the granulation near the limb. The normal non-magnetic granulation is compared to the abnormal granulation which we call magnetic. A new feature appearing for the first time at the extreme- limb of the disk (the last 100 km) is discussed in the context of the definition of the solar edge and of the solar diameter. A single sunspot is considered in order to illustrate how effectively the restoration works on the sunspot core. A set of 125 consecutive deconvolved images is assembled in a 45 min long movie illustrating the complexity of the dynamical behavior inside and around the sunspot.Comment: 15 pages, 22 figures, 1 movi

BESPRECHUNGEN COMPTES RENDUS - REVIEWS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72613/1/j.1467-6435.1957.tb00243.x.pd

Single and combined impacts of irradiation and surgery on lymphatic vasculature and fibrosis associated to secondary lymphedema

peer reviewedLymphedema (LD) refers to a condition of lymphatic dysfunction associated with excessive fluid accumulation, fibroadipose tissue deposition and swelling. In industrialized countries, LD development mainly results from a local disruption of the lymphatic network by an infection or cancer-related surgery (secondary LD). In the absence of efficient therapy, animal models are needed to decipher the cellular and molecular mechanisms underlying LD and test putative drugs. In this study, we optimized and characterized a murine model of LD that combines an irradiation of the mice hind limb and a radical surgery (lymph node resection associated to lymphatic vessel ligation). We investigated the respective roles of irradiation and surgery in LD formation by comparing their impacts, alone or in combination (with different intervention sequences), on eight different features of the pathology: swelling (paw thickness), indocyanine green (ICG) clearance, lymphatic vasculature remodeling, epidermal and dermal thickening, adipocyte accumulation, inflammatory cell infiltration and collagen deposition. This study supports the importance of radiation prior to surgery to experimentally induce a rapid, severe and sustained tissue remodeling harboring the different hallmarks of LD. We provide the first experimental evidence for an excessive deposition of periostin (POSTN) and tenascin-C (TNC) in LD. Through a computerized method of digital image quantification, we established the spatial map of lymphatic expansion, as well as collagen, POSTN and TNC deposition in papillary and reticular dermis of lymphedematous skins. This mouse model is available to study the patho-physiology of LD and test potential therapeutic targets

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts