Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer

Maishi, Nako; Kojima, Hiroshi; Sato, Mariko; Nagao‐Kitamoto, Hiroko; Annan, Dorcas A.; Baba, Shogo; Hojo, Takayuki; Yanagiya, Masahiro; Ohba, Yusuke; Ishii, Genichiro; Masutomi, Kenkichi; Shinohara, Nobuo; Hida, Kyoko

doi:10.3390/ijms20184595

Cited by 10 publications

(11 citation statements)

References 39 publications

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“…At present, most studies on endothelial cells use HDMECs or human umbilical vein endothelial cells (HUVECs) [13] . Since HDMECs is prone to aging and has a limited number of divisions, it needs to be purchased again or separated from the tissue [14] .…”

Section: Discussionmentioning

confidence: 99%

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Immortalization of human dermal microvascular endothelial cells

Wang¹,

Zhang²,

Feng³

et al. 2021

Preprint

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Objectives : Microvascular endothelial cells (MECs) have been proved by increasing studies to play important roles in the process of endocrine, immune response, and pathogenic microorganism infection. However, most types of MECs have a limited number of divisions. Therefore, the immortalization of primary MECs may provide a better cell model for research. And the present research is aimed to establish an immortal human dermal microvascular endothelial cells (HDMECs). Methods : To immortalize HDMECs, the telomerase reverse transcriptase (hTERT) gene was transferred into the primary HDMECs by lentiviral infection. The passages of HDMECs transfected with hTERT or without hTERT were analyzed. At the same time, the relative telomerase activity and telomere length in HDMECs transfected with hTERT were detected by RT-PCR assay. And the β-galactosidase (β-GAL) activity in HDMECs transfected with hTERT was detected by ELISA kits. Finally, karyotype and tube formation analysis were used to evaluate the effects of transfection with hTERT on the characteristics of HDMECs. Results: The results showed that the number of passages of HDMECs transfected with hTERT was significantly increased. The telomerase activity of HDMECs transfected with hTERT gene was enhanced, and β-GAL activity was significantly reduced. Moreover, the transfection of hTERT gene has almost no effect on the karyotype and tube formation of HDMECs. Conclusion: These data indicate that transfection of hTERT gene could successfully enhance the cleavage ability of HDMECs, and the characteristics of hTERT-HDMECs remain almost unchanged.

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Section: Discussionmentioning

confidence: 99%

“…Telomerase is an enzyme responsible for maintaining the length of telomeres. Since telomerase is inactivated or not expressed in most somatic cells, the replication potential of the cell is limited [13] .…”

Section: Immortalizing Cells By Introducing Foreign Genes Into Cells Through Viruses Is a Commonly Used Methodsmentioning

confidence: 99%

Immortalization of human dermal microvascular endothelial cells

Wang¹,

Zhang²,

Feng³

et al. 2021

Preprint

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“…MS‐1 cells were cultured in Dulbecco's minimum essential medium (DMEM, Sigma‐Aldrich, St. Louis, Missouri) supplemented with 10% heat‐inactivated fetal bovine serum (FBS). Immortalized human microvascular endothelial cells (iHMVECs), 29 transducted with SV40 large T antigen and hTERT with lentivirus, were cultured in EGM‐2MV (Microvascular Endothelial Cell Growth Medium‐2, Lonza, Basel, Switzerland). Cells were cultured at 37°C in a humidified atmosphere containing 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

The oxidized‐LDL/LOX‐1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells

Tsumita

Maishi

Annan

et al. 2022

Intl Journal of Cancer

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Epidemiological relationships between cancer and cardiovascular diseases have been reported, but a molecular basis remains unclear. Some proteoglycans that strongly bind low‐density‐lipoprotein (LDL) are abundant both in atherosclerotic regions and in high metastatic‐tumor tissue. LDL retention is crucial for the initiation of atherosclerosis, although its contribution to malignancy of cancer is not known. In our study, we show the importance of the accumulation of LDL in tumor metastasis. We demonstrated that high metastatic‐tumor tissue contains high amounts of LDL and forms more oxidized LDL (ox‐LDL). Interestingly, lectin‐like ox‐LDL receptor 1 (LOX‐1), a receptor for ox‐LDL and a recognized key molecule for cardiovascular diseases, was highly expressed in tumor endothelial cells (TECs). Neutrophils are important for ox‐LDL formation. Since we observed the accumulation and activation of neutrophils in HM‐tumors, we evaluated the involvement of LOX‐1 in neutrophil migration and activation. LOX‐1 induced neutrophil migration via CCL2 secretion from TECs, which was enhanced by ox‐LDL. Finally, we show genetic manipulation of LOX‐1 expression in TECs or tumor stroma tended to reduce lung metastasis. Thus, the LOX‐1/ox‐LDL axis in TECs may lead to the formation of a high metastatic‐tumor microenvironment via attracting neutrophils.

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“…These ECs exhibited an extended life span and retained their characteristic endothelial morphology, endothelial marker expression, and tube formation ability. Hence, these h-imTECs could be a valuable tool for drug screening to develop novel therapeutic agents specific to TECs or functional biological assays in tumor angiogenesis research (53).…”

Section: Tumor-specific Endothelial Cellsmentioning

confidence: 99%

A New Antitumor Direction: Tumor-Specific Endothelial Cells

et al. 2021

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Targeting tumor blood vessels is an important strategy for tumor therapies. At present, antiangiogenic drugs are known to have significant clinical effects, but severe drug resistance and side effects also occur. Therefore, new specific targets for tumor and new treatment methods must be developed. Tumor-specific endothelial cells (TECs) are the main targets of antiangiogenic therapy. This review summarizes the differences between TECs and normal endothelial cells, assesses the heterogeneity of TECs, compares tumorigenesis and development between TECs and normal endothelial cells, and explains the interaction between TECs and the tumor microenvironment. A full and in-depth understanding of TECs may provide new insights for specific antitumor angiogenesis therapies.

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Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer

Cited by 10 publications

References 39 publications

Immortalization of human dermal microvascular endothelial cells

Immortalization of human dermal microvascular endothelial cells

The oxidized‐LDL/LOX‐1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells

A New Antitumor Direction: Tumor-Specific Endothelial Cells

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