What is normal? Apelin and
            <scp>VEGFA</scp>
            , drivers of tumor vessel abnormality

Claesson‐Welsh, Lena

doi:10.15252/emmm.201910892

Cited by 5 publications

(11 citation statements)

References 9 publications

(13 reference statements)

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“…The results of our study fit with previous in vivo observations made, where ectopic apelin overexpression enhanced angiogenesis and tumor cell proliferation in subcutaneous tumor models [26,48,49]. Moreover, recent results obtained in a mouse model of breast cancer showed that loss-of-APLN markedly reduced tumor angiogenesis leading to impaired tumor growth and, consequently, improved survival of these animals [50,51].…”

Section: Discussionsupporting

confidence: 91%

Apelin Controls Angiogenesis-Dependent Glioblastoma Growth

Frisch

Kälin

Monk

et al. 2020

IJMS

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Glioblastoma (GBM) present with an abundant and aberrant tumor neo-vasculature. While rapid growth of solid tumors depends on the initiation of tumor angiogenesis, GBM also progress by infiltrative growth and vascular co-option. The angiogenic factor apelin (APLN) and its receptor (APLNR) are upregulated in GBM patient samples as compared to normal brain tissue. Here, we studied the role of apelin/APLNR signaling in GBM angiogenesis and growth. By functional analysis of apelin in orthotopic GBM mouse models, we found that apelin/APLNR signaling is required for in vivo tumor angiogenesis. Knockdown of tumor cell-derived APLN massively reduced the tumor vasculature. Additional loss of the apelin signal in endothelial tip cells using the APLN-knockout (KO) mouse led to a further reduction of GBM angiogenesis. Direct infusion of the bioactive peptide apelin-13 rescued the vascular loss-of-function phenotype specifically. In addition, APLN depletion massively reduced angiogenesis-dependent tumor growth. Consequently, survival of GBM-bearing mice was significantly increased when APLN expression was missing in the brain tumor microenvironment. Thus, we suggest that targeting vascular apelin may serve as an alternative strategy for anti-angiogenesis in GBM.

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Section: Discussionsupporting

confidence: 91%

Apelin Controls Angiogenesis-Dependent Glioblastoma Growth

Frisch

Kälin

Monk

et al. 2020

IJMS

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“…Apelin is an emerging endogenous ligand, which has attracted the attention of researchers because of its role in angiogenesis [9,13,14,26]. Previous studies have revealed that Apelin expression is up-regulated in various human solid tumors [13,26].…”

Section: Discussionmentioning

confidence: 99%

“…The bioactive peptide Apelin is an emerging endogenous ligand, which binds to the human G proteincoupled receptor APJ [8]. Apelin is a member of the adipokine family that is secreted by adipose tissue, and its expression is also observed in various cell types [9]. The Apelin gene encodes a prepropeptide consisting of 77 amino acids that may promote proteolytic maturation and subsequently generate different bioactive peptide fragments: Apelin-17, Apelin-36 and Apelin-13 that are the predominant types in the human plasma [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Apelin is a member of the adipokine family that is secreted by adipose tissue, and its expression is also observed in various cell types [9]. The Apelin gene encodes a prepropeptide consisting of 77 amino acids that may promote proteolytic maturation and subsequently generate different bioactive peptide fragments: Apelin-17, Apelin-36 and Apelin-13 that are the predominant types in the human plasma [8,9]. Apelin/APJ signaling pathway, which is widely expressed in the cardiovascular system, has been reported to be involved in various physiological and pathological processes such as angiogenesis, heart failure, energy metabolism and cancer progression [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…The Apelin gene encodes a prepropeptide consisting of 77 amino acids that may promote proteolytic maturation and subsequently generate different bioactive peptide fragments: Apelin-17, Apelin-36 and Apelin-13 that are the predominant types in the human plasma [8,9]. Apelin/APJ signaling pathway, which is widely expressed in the cardiovascular system, has been reported to be involved in various physiological and pathological processes such as angiogenesis, heart failure, energy metabolism and cancer progression [9,10]. The dysfunctional, abnormal vasculature morphology plays a signi cant role in the growth and development of tumor [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Apelin Is Associated with Proliferation and Angiogenesis in Gastric Cancer

Tian

Liu

Zhang

et al. 2020

Preprint

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Background: Apelin is an emerging endogenous ligand, which is involved in proliferation and angiogenesis in certain cancers. However, few studies have reported its functions and underlying mechanisms in human gastric cancer (GC). Therefore, the present study aimed to investigate the effect of Apelin expression in human GC and the underlying mechanisms of Apelin in the promotion of proliferation both in vitro and in vivo.Methods: A total of 178 patients diagnosed with GC under postoperative care were enrolled for the study to investigate clinicopathological and immunohistochemical factors of Apelin expression. Survival of patients was analyzed using the Kaplan-Meier method and Cox regression model. We adopted quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA to analyze human GC specimens and cell lines. The role and mechanisms of Apelin were evaluated by performing in vitro and in vivo experiments to analyze exogenous Apelin and its overexpression in human GC cells. Results: The expression of Apelin was higher in human gastric cancer cells than in adjacent normal tissues. Apelin, which was overexpressed in vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) status (P <0.05), pathological type (P <0.05) and nerve invasion (P <0.05), also exhibited a positive correlation with vascular endothelial growth factor (VEGF). Apelin overexpression or exogenous Apelin activated downstream of ERK/Cyclin D1/MMP-9 signaling pathway to promote MGC-803 cell proliferation and invasion in vitro. Apelin overexpression promoted angiogenesis aiming at accelerating growth of subcutaneous xenograft in vivo.Conclusions: This study has elucidated the relationship between Apelin and its clinicopathological features in human GC, and the role of Apelin in tumor cell proliferation in human GC cell lines. This is the first study to elucidate underlying mechanisms of Apelin in the proliferation of GC. Apelin can be a potential therapeutic target for human GC.

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Roles of apelin/APJ system in cancer: Biomarker, predictor, and emerging therapeutic target

Chen

Zhao

et al. 2022

Journal Cellular Physiology

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Cancer is a disease that seriously endangers human health and is mainly characterized by a high metastasis rate, a high recurrence rate, and a high mortality rate. The treatment of cancer has always been an important research direction of scientific research. A number of studies have shown that the apelin/APJ system is involved in the development and poor prognosis of a variety of cancers, such as lung cancer, liver cancer, cholangiocarcinoma, breast cancer, glioblastoma, prostate cancer, ovarian cancer, and so on. Accumulating evidence has also shown that the apelin/APJ system acts as a biomarker and predictor of postoperative effects in multiple cancers, which can also affect the tumor microenvironment and the efficacy of cancer immunotherapy. Considering that the apelin/APJ system may be a potential target for cancer treatment, it is of great significance for the study of new cancer treatment targets. To better understand the role of the apelin/APJ system on the occurrence and development of cancer, this article reviews the role of the apelin/APJ system in the occurrence and development of various cancers, angiogenesis, tumor stem cells, tumor microenvironment, drug resistance, poor prognosis, and the research progress of related anticancer drugs.

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What is normal? Apelin and VEGFA , drivers of tumor vessel abnormality

Cited by 5 publications

References 9 publications

Apelin Controls Angiogenesis-Dependent Glioblastoma Growth

Apelin Controls Angiogenesis-Dependent Glioblastoma Growth

Regulation of Apelin Is Associated with Proliferation and Angiogenesis in Gastric Cancer

Roles of apelin/APJ system in cancer: Biomarker, predictor, and emerging therapeutic target

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