Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells.
Yuquan Xiong,Hui-Chuan Sun,Wei Zhang,Xiao-Dong Zhu,Peng-Yuan Zhuang,Ju-Bo Zhang,Lu Wang,Wei-Zhong Wu,Lun-Xiu Qin,Zhao-You Tang +9 more
TLDR
TECs possessed enhanced angiogenic activity and resistance to chemotherapeutic drugs and an angiogenesis inhibitor, and may provide a better tool for studying tumorAngiogenesis and antiangiogenesis drugs in HCC.Abstract:
Purpose: Increasing evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype compared with endothelial cells (NEC) from adjacent normal tissue and may be able to acquire resistance to drugs. The aim of this study was to investigate the angiogenesis activity and response to drug treatment of TECs and NECs derived from human hepatocellular carcinoma (HCC). Experimental Design: TECs or NECs were isolated from HCC or adjacent normal liver tissue using anti-CD105 antibody coupled to magnetic beads. The phenotypic and functional properties of endothelial cells were characterized by testing the expression of CD105, CD31, CD144, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and von Willebrand factor, and the ability of DiI-Ac-LDL-uptake and tube formations. CD105 + TECs were compared with CD105 + NECs and human umbilical vein endothelial cells (HUVEC) by examining their ability to proliferate, motility, ability to adhere to tumor cells, response to tumor conditioned medium, and reactions to the chemotherapy drugs Adriamycin and 5-fluorouracil and the antiangiogenic drug sorafenib. Results: Compared with CD105 + NECs and HUVECs, CD105 + TECs showed increased apoptosis resistance and motility and proangiogenic properties. Meanwhile, CD105 + TECs had a greater ability to adhere to tumor cells and survive in the tumor environment. Moreover, CD105 + TECs acquired more resistance to Adriamycin, 5-fluorouracil, and sorafenib than CD105 + NECs and HUVECs. Conclusions: TECs possessed enhanced angiogenic activity and resistance to chemotherapeutic drugs and an angiogenesis inhibitor, and may provide a better tool for studying tumor angiogenesis and antiangiogenesis drugs in HCC.read more
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References
More filters
Journal ArticleDOI
Angiogenesis in cancer, vascular, rheumatoid and other disease
TL;DR: Think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth, which may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
Journal ArticleDOI
Mechanisms of angiogenesis and arteriogenesis.
TL;DR: The cellular and molecular mechanisms underlying the formation of endothelium-lined channels and their maturation via recruitment of smooth muscle cells (arteriogenesis) during physiological and pathological conditions are summarized, alongside with possible therapeutic applications.
Journal ArticleDOI
A Randomized Trial of Bevacizumab, an Anti–Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer
James Chih-Hsin Yang,Leah R. Haworth,Richard M. Sherry,Patrick Hwu,Douglas J. Schwartzentruber,Suzanne L. Topalian,Seth M. Steinberg,Helen X. Chen,Steven A. Rosenberg +8 more
TL;DR: Bvacizumab can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer, and this trial was stopped after the interim analysis met the criteria for early stopping.
Journal ArticleDOI
Molecular regulation of vessel maturation.
TL;DR: The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function.
Journal ArticleDOI
Angiogenesis: an organizing principle for drug discovery?
TL;DR: Viewing the process of angiogenesis as an 'organizing principle' in biology, intriguing insights into the molecular mechanisms of seemingly unrelated phenomena might be gained for the clinical use ofAngiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but also for developing therapeutic approaches for various diseases that are otherwise unrelated to each other.