scholarly journals Mechanisms and Clinical Significance of Tumor Lymphatic Invasion

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2585
Author(s):  
Noriki Fujimoto ◽  
Lothar C. Dieterich
Keyword(s):  
Tumor Cells ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Lymphatic Invasion ◽  
Malignant Cells ◽  
Single Tumor ◽  
Draining Lymph Nodes ◽  
Gain Access

Tumor-associated lymphatic vessels play an important role in tumor progression, mediating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes “hijacked” by tumor cells to gain access to the lymphatic system. Furthermore, we summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

scholarly journals SKIN LYMPHATIC SYSTEM IN THE PATHOGENESIS OF ARTERIAL HYPERTENSION – REVIEW AND CRITIQUE

Lymphology ◽  
2021 ◽  
Vol 53 (3) ◽  
Author(s):  
A Chachaj ◽  
A Szuba
Keyword(s):  
Blood Pressure ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Salt Intake ◽  
Lymphatic Vessels ◽  
High Salt ◽  
Large Reservoir ◽  
Inactive Form ◽  
High Salt Intake ◽  
Factor C

Although numerous studies have confirmed the relationship between high salt intake and elevated blood pressure, the exact molecular mechanisms of this relationship are still unclear. There is growing evidence that skin interstitium, as well as the skin lymphatic system, are important regulators of both sodium (Na+) balance and blood pressure. Skin is in itself a large reservoir of Na+ ions which are stored in an osmotically inactive form on glycosaminoglycans (GAGs). Local hypertonicity due to extensive accumulation of Na+ within the skin as a result of a high-salt diet was demonstrated to induce macrophages to express a transcription factor termed tonicity-responsive enhancer binding protein (TonEBP) and subsequently to secrete vascular endothelial growth factor-C (VEGF-C), activating lymphangiogenesis within the skin. This regulatory axis seems to be adaptive in maintaining blood pressure in high salt-load states. Recent studies have added new insights into the functioning of lymphatic vessels and the pathogenesis of salt-sensitive hypertension as well as questioned the classic view of Na+ homeostasis. This review aims to summarize recent findings pertaining to the involvement of the skin lymphatic system in Na+ and blood pressure regulation.

The biology and prognostic value of lymphatic vessel density (LD) and lymphatic invasion (LI) in regression in melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9017-9017
Author(s):  
S. Yun ◽  
P. Gimotty ◽  
W. Hwang ◽  
P. Dawson ◽  
P. VanBelle ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Value ◽  
Lymphatic Vessels ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymphocytic Infiltration ◽  
Melanoma Cells ◽  
Lymphatic Invasion ◽  
Complete Regression ◽  
Cox Models ◽  
Vertical Growth Phase

9017 Background: Regression in melanoma is characterized by increased vascularity, lymphocytic infiltrate and fibroplasia in the papillary dermis, accompanied by the absence (complete regression, CoR) or presence (partial regression, PaR) of melanoma cells in the epidermis. The prognostic value of regression is controversial. We noticed that LD and LI were increased in the areas of regression (AR) or areas with brisk lymphocytic infiltration (AB). Our goal was to clarify the prognostic value of regression in melanoma. Methods: Dual immunohistochemical staining was done using antibodies to podoplanin (lymphatic vessels) and S100 (melanoma cells) on paraffin tissues from 321 patients with vertical growth phase (VGP) primary melanomas who had 10 years or more of follow-up. LD in AR (both CoR and PaR) was compared with that of normal dermis adjacent and distant, as well as LD in the AB. LI in these areas was also scored. Unadjusted and adjusted hazard rates were obtained from univariate and multivariate Cox models for time to melanoma-specific death using established melanoma prognostic factors. Results: 116 patients (36%) had regression: 75 CoR (23%) and 41 PaR (13%). LD significantly decreased stepwise from CoR (mean ± se, 23.7 ± 2.7) to PaR (15.5 ± 1.1), adjacent normal dermis (7.3 ± 0.28) and distant normal dermis (5.4±0.31) and it was significantly elevated in the AB (18.5±0.78). Melanomas with CoR had the highest percentage of LI in both AR and AB. In addition, the percentage of LI in AB was highest for men and for those with VGP tumor infiltrating lymphocytes (TILs). Both high LD in AR and more LI in AB were associated with poor prognosis (p=0.004 and p=0.002, respectively). Six factors were significant in the final multivariate model: LI in AB (HR=2.3), LD in AR (HR=1.04), thickness (HR=1.44), axial (HR=7.7), ulceration (HR=2.5) and no VGP TILs (HR=2.8). Conclusions: AR and AB were associated with increased LD and higher incidence of LI in primary melanomas. LD and LI in AR or AB are independent prognostic factors. Our data suggest that the effects of regression on prognosis are mediated at least in part through lymphangiogenesis and LI. No significant financial relationships to disclose.

scholarly journals Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish

2018 ◽  
Author(s):  
Jingying Chen ◽  
Jianbo He ◽  
Qifen Yang ◽  
Yaoguang Zhang ◽  
Lingfei Luo
Keyword(s):  
Blood Vessels ◽  
Brain Edema ◽  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
Lymphatic Invasion ◽  
Brain Parenchyma ◽  
Genetic Ablation ◽  
Vascular Regeneration ◽  
Promising Therapeutic Approach

SUMMARYDamage to regional cerebrovascular network and neuronal tissues occurs during acute cerebrovascular diseases, such as ischemic stroke. The promotion of vascular regeneration is the most promising therapeutic approach. To understand cellular and molecular mechanisms underlying brain vascular regeneration, we developed two zebrafish cerebrovascular injury models using genetic ablation and photochemical thrombosis. Although brain parenchyma is physiologically devoid of lymphatic vasculature, we found that cerebrovascular injuries induce rapid ingrowth of meningeal lymphatics into the injured parenchyma. The ingrown lymphatics on one hand become lumenized drain interstitial fluid to resolve brain edema, on the other hand act as “growing tracks” for nascent blood vessels. The ingrown lymphatic vessels undergo apoptosis and clearance after cerebrovascular regeneration. This study reveals a pathological function of meningeal lymphatics, through previously unexpected ingrowth into brain parenchyma and a newly identified lymphatic function as vascular “growing tracks”.HIGHLIGHTSCerebrovascular injuries induce lymphatic ingrowth into the injured brain parenchyma The ingrown lymphatics drain interstitial fluid to resolve brain edema Nascent blood vessels use the ingrown lymphatic vessels as “growing tracks” The ingrown lymphatic vessels undergo apoptosis after vascular regeneration completes

scholarly journals Neutrophil Interactions with the Lymphatic System

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2106
Author(s):  
Arnolda Jakovija ◽  
Tatyana Chtanova
Keyword(s):  
Lymph Nodes ◽  
Lymphatic System ◽  
Neutrophil Migration ◽  
Lymphatic Vessels ◽  
High Endothelial Venules ◽  
Microbial Infections ◽  
Lymphatic Vasculature ◽  
Pathogen Control ◽  
Secondary Lymphoid Organs ◽  
Draining Lymph Nodes

The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues. In this review, we discuss the significance of neutrophil migration to secondary lymphoid organs and within the lymphatic vasculature and highlight emerging evidence of the neutrophils’ role in lymphangiogenesis.

scholarly journals The Diagnostic And Prognostic Value of DYNLL1 And RAN In Lung Adenocarcinoma

2021 ◽  
Author(s):  
Lei Cao ◽  
Hongsheng Liu ◽  
Zhili Cao ◽  
Naixin Liang ◽  
Chao Gao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Normal Lung ◽  
Using Data ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Lung adenocarcinoma (LUAD) is the most heterogeneous and aggressive among all NSCLC subtypes. This work aimed to determine the predictive ability of DYNLL1 and RAN in LUAD, as well as to explore the role of possible DYNLL1 and Ran molecular mechanisms on LUAD malignant behavior.Methods: Using data from the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of DYNLL1 and its related gene RAN in LUAD and normal lung tissues. We also studied the prognostic value of DYNLL1 and RAN in terms of overall survival (OS) in LUAD, liver cancer and renal cancer patients. Using data from the online database STRING, we further investigated the protein–protein interaction (PPI), miRNA and transcription factor regulatory networks of DYNLL1 and Ran. Then, molecular docking was used to obtain accurate combination models between molecular compounds and DYNLL1 or Ran. We also studied whether DYNLL1 and RAN influence the proliferation and migration of tumor cells with the stable knockdown LUAD cell lines.Results: The expression of DYNLL1 and RAN was significantly upregulated in LUAD tissues compared to normal controls. And high expressions of DYNLL1 and RAN were associated with unfavorable overall survival in LUAD patients. We also found that knockdown of DYNLL1 and RAN inhibit the proliferation and migration of A549 tumor cells.Conclusions: Overall, our study provides evidence that DYNLL1 and RAN are essential for the progression of LUAD. And they may serve as potential tumor biomarkers for the diagnosis and prognosis of patients with LUAD.

scholarly journals Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2061
Author(s):  
Louise A. Johnson ◽  
David G. Jackson
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Immune Cell ◽  
Cell Entry ◽  
Future Perspectives ◽  
Junctional Permeability ◽  
Immune Cell Migration ◽  
Critical Process ◽  
Draining Lymph Nodes

Entry to the afferent lymphatics marks the first committed step for immune cell migration from tissues to draining lymph nodes both for the generation of immune responses and for timely resolution of tissue inflammation. This critical process occurs primarily at specialised discontinuous junctions in initial lymphatic capillaries, directed by chemokines released from lymphatic endothelium and orchestrated by adhesion between lymphatic receptors and their immune cell ligands. Prominent amongst the latter is the large glycosaminoglycan hyaluronan (HA) that can form a bulky glycocalyx on the surface of certain tissue-migrating leucocytes and whose engagement with its key lymphatic receptor LYVE-1 mediates docking and entry of dendritic cells to afferent lymphatics. Here we outline the latest insights into the molecular mechanisms by which the HA glycocalyx together with LYVE-1 and the related leucocyte receptor CD44 co-operate in immune cell entry, and how the process is facilitated by the unusual character of LYVE-1 • HA-binding interactions. In addition, we describe how pro-inflammatory breakdown products of HA may also contribute to lymphatic entry by transducing signals through LYVE-1 for lymphangiogenesis and increased junctional permeability. Lastly, we outline some future perspectives and highlight the LYVE-1 • HA axis as a potential target for immunotherapy.

scholarly journals Podoplanin: a Prognostic Marker and a Potential Target for Therapy in Bladder Cancer

2020 ◽  
Vol 70 (12) ◽  
pp. 4393-4399
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Lymphatic Vessels ◽  
Lymphatic Invasion ◽  
High Rate ◽  
Invasive Bladder Cancer ◽  
Expression Clone ◽  
Response To Chemotherapy ◽  
Keywords Bladder Cancer ◽  
Podoplanin Expression

Invasive bladder cancer is a frequent neoplastic diseases, and despite progresses made in early diagnosis and surgical procedures, the outcome of patients is characterized by high rate of mortality. This is mainly due to the lack of response to chemotherapy and radiotherapy, and other new resources are limited. In the present work we analyzed 50 consecutive cases of invasive bladder cancer treated by open surgery. Specimens were processed using standard histological procedures, including establishment of the histological diagnosis and grading. Additional slides were stained for podoplanin expression, clone D2-40 to investigate the structure and number of lymphatic vessels. We found lymphatic vessels in both intra- and peritumor areas, showing significant differences in morphology and number. Lymphatic invasion by tumor cells was higher in peritumor than in intratumor vessels. Lymphatic microvessel density correlated with stage and grade of the tumor. Of interest is the expression of podoplanin by tumor cells of urothelial carcinoma in about 14% of the cases, with strong correlation with grading. Based on our results, expression of podoplanin in invasive bladder cancer might indicate three potential targets: lymphatics, myofibroblasts, and tumor cells in selected cases. Keywords: bladder cancer, immunohistochemistry, podoplanin, therapeutic target

scholarly journals Lymphatic endothelium

2003 ◽  
Vol 163 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Michael S. Pepper ◽  
Mihaela Skobe
Keyword(s):  
Tumor Cells ◽  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
Traditional View ◽  
Lymphatic Endothelium ◽  
Point Of Entry ◽  
Recent Advances ◽  
And Function

The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins, and is an important point of entry for leukocytes and tumor cells. The traditional view that lymphatic capillaries are passive participants in these tasks is currently being challenged. This overview highlights recent advances in our understanding of the molecular mechanisms underlying the formation and function of lymphatic vessels.

scholarly journals Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew K. Siggins ◽  
Nicola N. Lynskey ◽  
Lucy E. Lamb ◽  
Louise A. Johnson ◽  
Kristin K. Huse ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cancer Cells ◽  
Streptococcus Pyogenes ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Systemic Infection ◽  
Intracellular Pathogen ◽  
Infection Site ◽  
Local Infection ◽  
Draining Lymph Nodes

Abstract Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we show S. pyogenes remain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream for S. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.

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