Advertisement

Topics

Asparaginyl endopeptidase induces endothelial permeability and tumor metastasis via downregulating zonula occludens protein ZO-1.

08:00 EDT 13th May 2019 | BioPortfolio

Summary of "Asparaginyl endopeptidase induces endothelial permeability and tumor metastasis via downregulating zonula occludens protein ZO-1."

Zona occludens-1 (ZO-1) is a key component of tight junctions that govern the function of the endothelial barrier against tumor metastasis. Factors secreted by tumor cells contribute to the maintenance of tumor vascular networks. How tumor cell-derived protein signals regulate ZO-1 expression is unclear. Here, we explored the effect of tumor cell-secreted asparaginyl endopeptidase (AEP) on the permeability of endothelial cells in the tumor microenvironment. First, we confirmed the existence of AEP in conditioned medium (CM) from AEP-overexpressing MDA-MB-231 and 4 T1 cells. Treatment with CM from AEP-overexpressing tumor cells increased the permeability and tumor cell transversal of an endothelial monolayer. Furthermore, CM from AEP-overexpressing tumor cells suppressed endothelial ZO-1 expression, as well as ZO-1-associated nucleic acid binding protein ZONAB. In addition, the level of phosphorylated STAT3 was increased by treatment with AEP-containing CM. A mutation of RGD or blocking integrin αvβ3 with antibody recovered the ZO-1 downregulation induced by AEP. In vivo, a lung metastatic mouse model showed increased endothelial permeability in the AEP-overexpressing group compared with the control group. An orthotopic tumor transplantation model was established using AEP-overexpression and compared with mice receiving control 4 T1 cells. Compared with controls, overexpression of AEP increased lung metastatic foci and area, as well as vascular instability in primary tumors or lung metastatic sites. Moreover, endothelial ZO-1 was decreased in the AEP-overexpressing group. Taken together, our data show that tumor cell-derived AEP increases the permeability of endothelial barriers. Interactions between RGD and endothelial integrin αvβ3 mediate this effect by downregulating ZO-1.

Affiliation

Journal Details

This article was published in the following journal.

Name: Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Pages:

Links

DeepDyve research library

PubMed Articles [11700 Associated PubMed Articles listed on BioPortfolio]

The unconventional role of Akt1 in the advanced cancers and in diabetes-promoted carcinogenesis.

Decades of research have elucidated the critical role of Akt isoforms in cancer as pro-tumorigenic and metastatic regulators through their specific effects on the cancer cells, tumor endothelial cells...

Galectin-8 induces endothelial hyperpermeability through the eNOS pathway involving S-nitrosylation-mediated adherens junction disassembly.

The permeability of endothelial cells is regulated by the stability of the adherens junctions, which is highly sensitive to kinase-mediated phosphorylation and nitric oxide synthase (eNOS)-mediated S-...

ALK7 Signaling Manifests a Homeostatic Tissue Barrier That Is Abrogated during Tumorigenesis and Metastasis.

Herein, we report that the TGFß superfamily receptor ALK7 is a suppressor of tumorigenesis and metastasis, as revealed by functional studies in mouse models of pancreatic neuroendocrine and luminal b...

Tumor Metastasis in the Microcirculation.

Tumor cell metastasis through blood circulation is a complex process and is one of the great challenges in cancer research as metastatic spread is responsible for ∼90% of cancer-related mortality. T...

Contiguous Metastasis of Pulmonary Adenocarcinoma to Meningioma.

 Metastasis from one tumor into another is known as tumor-to-tumor metastasis. We report a case of a contiguous occurrence of meningioma and brain cancer metastasis.

Clinical Trials [7697 Associated Clinical Trials listed on BioPortfolio]

the Influence of General Anesthesia on Tumor Metastasis and Recurrence

The purpose of this study was to investigate whether general anesthesia will affect the postoperative recurrence and metastasis of malignant tumor.

The Effect of a Cranberry Beverage on Intestinal Permeability and Gastrointestinal Function in Generally Healthy Adults

In this double blind, crossover study participants will consume a cranberry beverage and a cranberry-flavored beverage for 2 weeks each. Gut permeability will be assessed weekly using aspi...

Endothelial Injury Mechanism of in Elderly Patients Undergoing Major Surgery

The incidence of postoperative cognitive injury is high in elderly patients, especially after major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible ...

Prognostic Value of Tumor Thickness of Buccal Mucosa Squamous Cell Carcinoma on the Incidence of Nodal Metastasis.

Does the tumor thickness value of buccal squamous cell carcinomas, predict cervical nodal metastasis in clinically and radio-graphical neck negative (N0) thus sparing such patients unneces...

Intestinal Permeability in Obesity

In rodents, obesity is associated with changes in tight junctions' structure in small intestine, which impacts intestinal permeability and results in metabolic complications. Few data exis...

Medical and Biotech [MESH] Definitions

The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.

A cell adhesion molecule of the immunoglobulin superfamily that is expressed by ENDOTHELIAL CELLS where it functions to stabilize INTERCELLULAR JUNCTIONS. It is also highly expressed by melanoma tumor cells and may facilitate their METASTASIS.

Hypoxic conditions in tumor cells due to the tumor outgrowing its blood supply. It is associated with increased METASTASIS and resistance to RADIOTHERAPY and DRUG THERAPY.

A member of tumor necrosis factor superfamily found on ENDOTHELIAL CELLS that plays a role in the inhibition of endothelial cell growth and PHYSIOLOGIC ANGIOGENESIS.

Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...


Searches Linking to this Article