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Altered phenotype of lymphatic endothelial cells induced by highly metastatic OTSCC cells contributed to the lymphatic metastasis of OTSCC cells.

The lymphatic endothelial cell (LEC) is an interactive surface for cancer cells. This article aims to explore cancer cell-induced changes of LEC, and study the tumor-lymphatic endothelium interaction. Here, LECs were co-cultured with highly and poorly metastatic tongue cancer cells. The differences in biologic behaviors and gene expression profiles between them were examined. The results showed that LECs induced by highly metastatic cancer cells displayed abnormal biologic behaviors, and could secrete chemokines to promote the migration of cancer cells. Therefore, biologic properties and funct

M2 macrophages promote lymphatic metastasis by regulating PKM2 nuclear translocation in triple-negative breast cancer.

Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, is characterised by poor prognosis and frequent lymph node … ally activates the lymphatic growth factors VEGFC/D. VEGFC/D subsequently stimulates VEGF-dependent lymphangiogenesis, accelerating metastasis. Pharmacological PKM2 inhibition blocked PKM2 phosphorylation/nuclear translocation and suppressed VEGFC/D expression, thereby attenuating LNM. Clinically, high M2 macrophage infiltration correlated with a shorter disease-fr …

A lymphatic organ-on-a-chip reveals flow-responsive LEC paracrine signals promoting BMSC osteogenesis in jawbone regeneration.

The lymphatic system is essential for fluid homeostasis and immune surveillance, yet its role in skeletal regeneration remains poorly define … ine molar extraction model with controlled occlusal loading revealed that occlusal loading promoted lymphangiogenesis and accelerated alveolar bone regeneration, accompanied by elevated WISP1 expression within alveolar sockets. Conversely, pharmacological suppression of lymphatic expansion through MAZ51 administration impaired bone formation while reducing WISP1 le …

Lymphatic Vessel Density or Area Are Not Reliable Prognostic Factors in Oral Cancer.

BACKGROUND: Oral tongue squamous cell carcinomas (OTSCC) frequently metastasise via lymphatic vessels, thus lymphangiogenesis may enhance tumour cell dissemination by increasing tumour-lymphatic interactions. The prognostic significance of lymphatic vessel density (LVD) and lymphatic vessel area (LVA) in OTSCC remains inconclusive. This study aimed to evaluate the association of tumour-associated LVD and LVA with clinical outcomes and pathological characteristics in a homogenous OTSCC cohort. METHODS: We analysed tumour samples from 121 OTSCC patients using D2-40 immunohistochemical staining …

Hypoxia Impairs Migration of Human Dermal Lymph Endothelial Cells: Implications for Lymphedema Pathogenesis.

Introduction: Lymphedema, characterized by abnormal lymph circulation, is a chronic debilitating condition often associated with chronic inf … tion, potentially exacerbating lymphedema. Protecting vasa vasorum may preserve HDLEC migration and lymphangiogenesis. Further exploration of hypoxia-HDLEC interactions is crucial for understanding lymphedema pathogenesis and developing therapies.

Vascular Endothelial Growth Factor-C Treatment Enhances Cerebrospinal Fluid Outflow during Toxoplasma gondii Brain Infection but Does Not Improve Cerebral Edema.

Cerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergen … with a vascular endothelial growth factor (VEGF)-C-expressing viral vector, which induced meningeal lymphangiogenesis and improved CSF outflow in chronically infected mice. No difference in cerebral edema was observed between mice that received VEGF-C and those that rececived sham treatment. Therefore, although VEGF-C treatment can improve lymphatic outflow in mice …

Receptor Activity Modifying Protein RAMP Sub-Isoforms and Their Functional Differentiation, Which Regulates Functional Diversity of Adrenomedullin.

AM knockout (AM-/-) and RAMP2 knockout (RAMP2-/-) proved lethal for mice due to impaired embryonic vascular development. Although most vascu … 2 is essential for maintaining cardiac mitochondrial function, while RAMP3 is essential for cardiac lymphangiogenesis. Transplantation of cancer cells into drug-inducible vascular endothelial cell-specific RAMP2 knockout mice resulted in enhanced metastasis to distant organs, whereas metastasis was suppressed in RAMP3-/- mice. RAMP2 suppresses cancer metastasis by …

Effect of VEGFC on lymph flow and inflammation-induced alveolar bone loss.

The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The … no-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ /αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ /αSMA- lymphatic capillaries are increased, whereas LYVE1+ /αSMA+ collec …

Prevention of postsurgical lymphedema via immediate delivery of sustained-release 9-cis retinoic acid to the lymphedenectomy site.

BACKGROUND AND OBJECTIVES: Previously, we have shown that 9-cis retinoic acid (9-cis RA) stimulates lymphangiogenesis and limits postsurgical lymphedema in animal models when administered via daily intraperitoneal injections. In this study, we investigate whether a single-use depot 9-cis RA drug delivery system (DDS) implanted at the site of lymphatic injury can mitigate the development of lymphedema in a clinically relevant mouse limb model. METHODS: Hind limb lymphedema was induced via surgical lymphadenectomy and irradiation. Animals were divided into two treatment groups: (1) 9-cis RA DDS…

Cytoplasmic neuropilin 2 is associated with metastasis and a poor prognosis in early tongue cancer patients.

Neuropilin 2 (Nrp2) plays an important role in regulating lymphangiogenesis. Nrp2 expression in early tongue cancer was investigated to predict lymph node metastasis and the long-term prognosis. The relationships between clinicopathological variables of cT1-T2N0 tongue squamous cell carcinoma (SCC) and overexpression of Nrp2, vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 3 (VEGFR3), and semaphorin 3F (Sema3F) were analyzed. Expression levels were compared using oral SCC cell lines. The Nrp2 gene was silenced to determine the impact of Nrp2. Cytoplasm…

NLRP3 inflammasome as a therapeutic target in oral squamous cell carcinoma: implications for tumorigenesis and immunomodulation.

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy strongly influenced by chronic inflammation. Central to this pr … capabilities via pyroptosis induction. NLRP3 activation promotes epithelial-mesenchymal transition, lymphangiogenesis, and chemoresistance through signaling networks involving SOAT1, miR-22, and PRDX1. Additionally, it regulates the tumor immune microenvironment by modulating tumor-associated macrophages, neutrophils, and cytokines like IL-6 and IL-1β. Oral pathoge …

From repair to disease: lymphatic contributions to regeneration, cancer and ageing.

BACKGROUND: The lymphatic vasculature maintains tissue fluid homeostasis, lipid transport, and immune surveillance. Beyond these classical roles, lymphatic vessels regulate tissue development and repair through lymphangiocrine signalling, whereby lymphatic endothelial cells (LECs) secrete mediators such as Reelin, R-spondin-3, and CCL21 that modulate stem cell niches, immune trafficking, and regeneration. Ageing-associated lymphatic dysfunction, driven by LEC senescence, impaired lymphangiogenesis, and lymph node stromal remodelling, leads to defective tissue repair, chronic low-grade inflamma…

Gorham-Stout disease with thoracic involvement: pathogenic mechanisms, respiratory complications, and multimodal therapies.

BACKGROUND: Gorham-Stout disease (GSD), also known as vanishing bone disease, is a rare osteolytic disorder characterized by progressive bon … observed in over 40% of cases, with chylothorax accounting for the highest mortality risk. Aberrant lymphangiogenesis, immune dysregulation, and osteoclast hyperactivation formed the mechanistic triad driving disease progression. Imaging (CT/MRI/PET) and exclusion-based diagnostics remain essential. Sirolimus-based regimens, bisphosphonates, radiotherapy, and surgi …

MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.

Lymph node metastasis (LNM) is a pivotal determinant of poor prognosis in ovarian cancer (OC), yet how tumor-intrinsic programs remodel the … s fibroblasts into VEGF-C-secreting, alpha-smooth muscle actin (α-SMA)-positive CAFs that stimulate lymphangiogenesis and LNM; SPHK1 inhibition blunts these phenotypes, whereas S1P supplementation restores them. These findings provide novel insights into lymphatic metastasis and demonstrate that metastatic competence depends not only on intrinsic tumor aggressivene …

Comparison of Vascular Endothelial Growth Factor C Expression with Lymph Node Metastasis Status and Survival in Gastric Cancer.

INTRODUCTION: Lymph node metastasis is crucial in determining prognosis and treatment for gastric cancer. Vascular endothelial growth factor C (VEGF-C), known for its role in lymphangiogenesis, has been linked to metastasis in various cancers. This study investigated the correlation between VEGF-C expression, lymph node metastasis, and overall survival in gastric cancer patients. METHODS: This retrospective cohort study included 109 patients who underwent gastrectomy and D2 lymphadenectomy for gastric adenocarcinoma between 2011 and 2019. VEGF-C expression was evaluated via immunohistochemist…

Collagen Hydrogel Loaded With 9-cisRA-Lip Is an Option for Treatment of Secondary Lymphedema after Surgery.

Background: Secondary upper limb lymphedema commonly occurs after breast cancer surgery, for which treatment is limited. 9-cis-retinoic acid (9-cisRA) has been demonstrated to increase lymphangiogenesis without enhancing tumor metastasis but has disadvantages of poor water solubility, ready decomposition in light, instability to heat, and a short half-life. Methods: Based on this, 9-cisRA-Lip with a particle size of roughly 143 nm and high dispersibility was prepared by thin-film dispersion method and verified by Malvern Laser Particle Size Analyzer and electron microscopy. Results: In vitro, …

Mast cells: a novel therapeutic avenue for cardiovascular diseases?

Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve, and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodelling, and fibrosis. Mast cells release preformed mediators (e.g. histamine, tryptase, and chymase) and de novo synthesized mediators (e.g. cysteinyl leukotriene C4 and prostaglandin D2), as well as …

VEGFR3 Modulates Busic Permectability посредством контроля сигнала VEGFF/VEGFR2.

RATALE: Валютный эндотелиальный коэффициент роста (VEGFF) является основным движителем ангиогенеза и сосудистой проницаемости через рецептор VEGFF 2 (VEGFR2), в то время как сигналы лимфангиогенеза передаются через VEGFC/D через VEGFR3. VEGFR3 регулирует также рост ангиогенеза и кровеносных сосудов, но в какой степени VEGFR3 контролирует проницаемость кровеносных сосудов. ЦЕЛЬ: Изучение роли VEGFR3 в регулировании сосудистой проницаемости, вызванной VEGFR. МЕТОДЫ И РЕЗУЛЬТАТЫ: Долгосрочное глобальное исключение гена Вегфр3 у взрослых мышей привело к увеличению осаждения фибриногенов в легких и

Совпадение в аннотации оригинала
RATIONALE: Vascular endothelial growth factor (VEGF) is the main driver of angiogenesis and vascular permeability via VEGF receptor 2 (VEGFR2), whereas lymphangiogenesis signals are transduced by VEGFC/D via VEGFR3. VEGFR3 also regulates sprouting angiogenesis and blood vessel growth, but to what extent VEGFR3 signaling controls blood vessel permeability rem…

Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival.

PURPOSE: The lymphatic pathway mediates transplant rejection. We recently reported that lymphatic vessels develop luminal valves in the cornea during lymphangiogenesis, and these valves express integrin alpha 9 (Itga-9) and play a critical role in directing lymph flow. In this study, we used an allogeneic corneal transplantation model to investigate whether Itga-9 blockade could suppress valvulogenesis after transplantation, and how this effect would influence the outcomes of the transplants. METHODS: Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) an…

Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice.

Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-γ is a pro-inflammatory cytokine with anti- … Nγ, anti-fibrotic effects of Fibroferon were more pronounced. Unilateral ureter obstruction-induced lymphangiogenesis was significantly reduced by Fibroferon but not full-length IFNγ. In contrast to full-length IFNγ, Fibroferon did not induce IFNγ-related side-effects as evidenced by preserved low-level brain MHC II expression (similar to vehicle), lowered plasma t …