Regulation of lymphatic vascular morphogenesis: Implications for pathological - tumor lymphangiogenesis.

Feb 2013

Martinez-Corral I, Makinen T.

Source

Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.

Abstract

Lymphatic vasculature forms the second part of our circulatory system that plays a critical role in tissue fluid homeostasis. Failure of the lymphatic system can lead to excessive accumulation of fluid within the tissue, a condition called lymphedema. Lymphatic dysfunction has also been implicated in cancer metastasis as well as pathogenesis of obesity, atherosclerosis and cardiovascular disease. Since the identification of the first lymphatic marker VEGFR-3 and growth factor VEGF-C almost 20 years ago, a great progress has been made in understanding the mechanisms of lymphangiogenesis. This has been achieved largely through characterization of animal models with specific lymphatic defects and identification of genes causative of human hereditary lymphedema syndromes. In this review we will summarize the current understanding of the regulation of lymphatic vascular morphogenesis, focusing on mechanisms that have been implicated in both developmental and pathological (tumor) lymphangiogenesis.

Elsevier

Incorporating measured valve properties into a numerical model of a lymphatic vessel.

Feb 2013

Bertram CD, Macaskill C, Moore JE Jr.

Source

a School of Mathematics and Statistics, University of Sydney, New South , Wales , 2006 , Australia.

Abstract

An existing lumped-parameter model of multiple lymphangions (lymphatic vascular segments) in series is adapted for the incorporation of recent physiological measurements of lymphatic vascular properties. The new data show very marked nonlinearity of the passive pressure-diameter relation during distension, relative to comparable blood vessels, and complex valve behaviour. Since lymph is transported as a result of either the active contraction or the passive squeezing of vascular segments situated between two one-way valves, the performance of these valves is of primary importance. The valves display hysteresis (the opening and closing pressure drop thresholds differ), a bias to staying open (both state changes occur when the trans-valve pressure drop is adverse) and pressure-drop threshold dependence on transmural pressure. These properties, in combination with the strong nonlinearity that valve operation represents, have in turn caused intriguing numerical problems in the model, and we describe numerical stratagems by which we have overcome the problems. The principal problem is also generalised into a relatively simple mathematical example, for which solution detail is provided using two different solvers.

PubMed

Noonan syndrome.

Jan 2013

Roberts AE, Allanson JE, Tartaglia M, Gelb BD.

Source

Department of Cardiology and Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA. amy.roberts@cardio.chboston.org

Abstract

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS-MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype-phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments.

Science Direct

See also:

Noonan's Syndrome

A pathway for unicellular tube extension depending on the lymphatic vessel determinant Prox1 and on osmoregulation.

Jan 2013

Kolotuev I, Hyenne V, Schwab Y, Rodriguez D, Labouesse M.

Source

1] IGBMC, Development and Stem Cells Program, CNRS (UMR7104)/INSERM (U964)/Université de Strasbourg, 1 rue Laurent Fries, BP.10142, 67400 Illkirch, France [2].

Abstract

The mechanisms regulating the extension of small unicellular tubes remain poorly defined. Here we identify several steps in Caenorhabditis elegans excretory canal growth, and propose a model for lumen extension. Our results suggest that the basal and apical excretory membranes grow sequentially: the former extends first like an axon growth cone; the latter extends next as a result of an osmoregulatory activity triggering peri-apical vesicles (a membrane reservoir) to fuse with the lumen. An apical cytoskeletal web including intermediate filaments and actin crosslinking proteins ensures straight regular lumengrowth. Expression of several genes encoding proteins mediating excretory lumen extension, such as the osmoregulatory STE20-like kinase GCK-3 and the intermediate filament IFB-1, is regulated by ceh-26 (here referred to as pros-1), which we found essential for excretory canal formation. Interestingly, PROS-1 is homologous to vertebrate Prox1, a transcription factor controlling lymphatic vessel growth. Our findings have potential evolutionary implications for the origin of fluid-collecting organs, and provide a reference for lymphangiogenesis.

PubMed

Adiponectin receptor expression in gastric carcinoma: implications in tumor development and progression.

Jan 2013

Shin E, Park DJ, Kim HH, Won NH, Choe G, Lee HS.

Source

Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumiro, Bundang-gu, Seongnam, Gyeonggi, 463-707, South Korea.

Abstract

PURPOSE:

Adiponectin, an adipocyte-secreted endogenous insulin sensitizer, appears to play an important role in progression of several malignancies. Expression of adiponectin receptors-AdipoR1 and AdipoR2-has been documented in gastric cancer (GC) cell lines, but its role in GCs is still controversial. We investigated expression level of 2 adiponectin receptors and correlated their expression with prognosis in GC patients.

METHODS:

We immunohistochemically evaluated AdipoR1 and AdipoR2 expression in 59 non-neoplastic gastric mucosas, 48 gastric adenomas, 250 GCs, and 58 lymph nodes involved by metastatic GC and assessed its association with clinicopathologic characteristics.

RESULTS:

Expression rates of both receptors increased stepwise in non-neoplastic gastric mucosa, gastric adenoma, intestinal-type GC, and metastatic GC (p < 0.001). AdipoR1 and AdipoR2 expression was observed in 85 (34.0 %) and 118 (47.2 %) GC cases, respectively. Expression rates were higher in intestinal-type GC than in diffuse-type GC (p < 0.001 and 0.016, respectively). AdipoR1 and AdipoR2 expression was more frequent in advanced GC than in early GC (p < 0.001, each) and was associated with lymphatic invasion (p = 0.046 and 0.001, respectively). AdipoR2 expression was associated with poor overall and disease-free survival (p = 0.001 and 0.007, respectively). AdipoR1 expression was associated with poor disease-free survival for intestinal-type GC patients (p = 0.046). In multivariate analysis, AdipoR2 was an independent prognostic factor for intestinal-type GC (p = 0.017).

CONCLUSIONS:

Adiponectin receptor expression is related to GC development and progression, especially intestinal-type GC. Thus, adiponectin receptor expression can serve as a prognostic marker in GC patients.

Springer