Primary tumor‐secreted VEGF induces vascular hyperpermeability in premetastatic lung via the occludin phosphorylation/ubiquitination pathway

Li, Ranran; Qi, Yana; Jiang, Man; Zhang, Tiehong; Wang, Hongwei; Wang, Liguang; Han, Mingyong

doi:10.1002/mc.23120

Cited by 26 publications

(21 citation statements)

References 39 publications

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“…Several factors secreted by CSCs are involved in PMN formation. For example, VEGF increases vasculature permeability in the PMN [ 189 ] and stimulates MMP-9 expression in premetastatic tissue, thus facilitating tumor cell invasion [ 190 ]. Moreover, VEGF enhances the recruitment of bone marrow-derived cells (BMDCs), which are critical for PMN formation [ 191 , 192 ] and facilitate tumor-promoting microenvironment through CCL9 secretion, induced by TGF-ß signaling [ 193 ].…”

Section: Secretome In Metastasismentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and differentiated tumor cells, as well as different cell types, such as mesenchymal stem cells, endothelial cells, fibroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), different in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these factors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metastasis, resistance to antitumor treatments and their own maintenance by the secretion of different factors such as IL-6, VEGF and TGF-ß. Due to the strong influence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the first time the main components of the CSC secretome and how they mediate different tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.

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Section: Secretome In Metastasismentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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“…34,35 However, VEGFD interdiction not only inhibits pathological lymphangiogenesis but also suppresses healthy blood vessels. 36,37 On the basis of our findings, the SIRT2 expression is negatively correlated with the expression of VEGFD and lymphangiogenesis in the HNC cell, suggesting that reagent for SIRT2 might be helpful to inhibit tumor lymphangiogenesis. On the other side, EPAS1 regulates On the 25th day after injection, typical IHC staining images, the expression scores of VEGFD and SIRT2, and MVD count of Cal27 cells originated tumors were observed.…”

Section: Evidence For Sirt2-epas1 Interaction and Its Role In Tumormentioning

confidence: 61%

“…With an in‐depth comprehension of the inherent mechanism of lymphangiogenesis, agent targeting vessel pathway has been proposed as one of the most promising strategies in cancer therapy, and over the past 10 years, several antitumor lymphangiogenesis agents have been approved 34,35 . However, VEGFD interdiction not only inhibits pathological lymphangiogenesis but also suppresses healthy blood vessels 36,37 . On the basis of our findings, the SIRT2 expression is negatively correlated with the expression of VEGFD and lymphangiogenesis in the HNC cell, suggesting that reagent for SIRT2 might be helpful to inhibit tumor lymphangiogenesis.…”

Section: Discussionmentioning

confidence: 99%

SIRT2 modulates VEGFD‐associated lymphangiogenesis by deacetylating EPAS1 in human head and neck cancer

Yang

Liang

et al. 2020

Molecular Carcinogenesis

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Sirtuin 2 (SIRT2) is one of seven mammalian homologs of silent information regulator 2 (Sir2) and an NAD +-dependent deacetylase; however, its critical role in lymphangiogenesis remains to be explored. We investigate SIRT2 mediated regulation of vascular endothelial growth factor D (VEGFD) expression and lymphangiogenesis by deacetylating endothelial PAS domain protein 1 (EPAS1) in head and neck cancer (HNC) in vitro and in vivo. In this study, we report that SIRT2, rather than other members of the Sir2 family, reduces the expression of VEGFD and lymphangiogenesis in hypoxia-induced HNC cells and transplanted HNC mice models by reducing EPAS1 acetylation at Lys674 and decreasing the transcriptional activity of EPAS1 target genes. The expression of SIRT2 was closely related to the expression of VEGFD, lymphangiogenesis in subcutaneously transplanted mice models, and lymphangiogenesis in patients with HNC. Our results suggest that SIRT2 plays a central role in tumor lymphangiogenesis via deacetylating EPAS1 protein. Reagents targeting the NAD +-dependent deacetylase activity of SIRT2 would be beneficial for inhibiting tumor lymphangiogenesis and treating other hypoxia-related diseases.

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“…Angiogenic edema plays a key role in the occurrence and development of intractable brain edema. Vascular endothelial growth factor (VEGF) can significantly increase the vascular permeability of the tumor ( 17 ). Nassehi et al ( 18 ) found that the peritumoral edema index was positively correlated with the expression of the VEGF gene and VEGF-A protein.…”

Section: Discussionmentioning

confidence: 99%

The Value of Anlotinib in the Treatment of Intractable Brain Edema: Two Case Reports

Song

Sun

et al. 2021

Front. Oncol.

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About 20-30 percent of patients with cancer, such as non-small cell lung cancer, breast cancer, melanoma and renal cell carcinoma, will develop brain metastases (BM). Primary and secondary brain tumors are often accompanied by peritumoral edema. Due to the limited intracranial space, peritumoral edema will further increase the intracranial pressure and aggravate clinical symptoms. Radiotherapy, as a basic component of the treatment of intracranial tumors, induces blood vessel damage and aggravates brain edema. The combination of edema caused by the tumor itself and radiotherapy is collectively referred to as intractable brain edema. Edema can increase intracranial pressure and cause associated neurologic symptoms, which seriously affects the quality of life of patients. Steroids, specifically dexamethasone, have become the gold standard for the management of tumor-associated edema. However, steroids can lead to variety of adverse effects, including moon face, high blood pressure, high blood sugar, increased risk of infection, bone thinning (osteoporosis), and fractures, especially with prolonged use. The investigation of other types of drugs is urgently needed to address this problem.Compared to other anti-angiogenic agents, anlotinib acts on vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3 and FGFR4), platelet derived growth factor receptor (PDGFR) and stem cell factor receptor (c-kit) simultaneously. However, according to the literature retrieval, there are no studies on anlotinib for the treatment of intractable brain edema. We describe here two cases of brain edema and review the literature available and hope to discover new agents that are safer and more effective.

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Primary tumor‐secreted VEGF induces vascular hyperpermeability in premetastatic lung via the occludin phosphorylation/ubiquitination pathway

Cited by 26 publications

References 39 publications

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

SIRT2 modulates VEGFD‐associated lymphangiogenesis by deacetylating EPAS1 in human head and neck cancer

The Value of Anlotinib in the Treatment of Intractable Brain Edema: Two Case Reports

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