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The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model.
Hepatology. 2001 Apr; 33(4):841-7.Hep

Abstract

The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation.

Authors+Show Affiliations

Third Department of Internal Medicine, Nara Medical University, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11283848

Citation

Yoshiji, H, et al. "The Vascular Endothelial Growth Factor Receptor KDR/Flk-1 Is a Major Regulator of Malignant Ascites Formation in the Mouse Hepatocellular Carcinoma Model." Hepatology (Baltimore, Md.), vol. 33, no. 4, 2001, pp. 841-7.
Yoshiji H, Kuriyama S, Hicklin DJ, et al. The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model. Hepatology. 2001;33(4):841-7.
Yoshiji, H., Kuriyama, S., Hicklin, D. J., Huber, J., Yoshii, J., Ikenaka, Y., Noguchi, R., Nakatani, T., Tsujinoue, H., & Fukui, H. (2001). The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model. Hepatology (Baltimore, Md.), 33(4), 841-7.
Yoshiji H, et al. The Vascular Endothelial Growth Factor Receptor KDR/Flk-1 Is a Major Regulator of Malignant Ascites Formation in the Mouse Hepatocellular Carcinoma Model. Hepatology. 2001;33(4):841-7. PubMed PMID: 11283848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model. AU - Yoshiji,H, AU - Kuriyama,S, AU - Hicklin,D J, AU - Huber,J, AU - Yoshii,J, AU - Ikenaka,Y, AU - Noguchi,R, AU - Nakatani,T, AU - Tsujinoue,H, AU - Fukui,H, PY - 2001/4/3/pubmed PY - 2001/5/1/medline PY - 2001/4/3/entrez SP - 841 EP - 7 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 33 IS - 4 N2 - The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/11283848/The_vascular_endothelial_growth_factor_receptor_KDR/Flk_1_is_a_major_regulator_of_malignant_ascites_formation_in_the_mouse_hepatocellular_carcinoma_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270-9139(01)18721-5 DB - PRIME DP - Unbound Medicine ER -