Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: Implication of RRM2 in angiogenesis

Keqiang Zhang, Shuya Hu, Jun Wu, Linling Chen, Jianming Lu, Xiaochen Wang, Xiyong Liu, Bingsen Zhou, Yun Yen

Research output: Contribution to journalArticle

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Abstract

Background: In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2. Results: We examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts. Conclusion: These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.

Original languageEnglish
Article number11
JournalMolecular Cancer
Volume8
DOIs
Publication statusPublished - Feb 28 2009
Externally publishedYes

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Vascular Endothelial Growth Factor A
Thrombospondin 1
KB Cells
Neoplasms
Growth
Ribonucleotides
Ribonucleotide Reductases
In Vitro Techniques
Chemotaxis
Heterografts
Small Interfering RNA
Endothelial Cells
Neoplasm Metastasis
Messenger RNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo : Implication of RRM2 in angiogenesis. / Zhang, Keqiang; Hu, Shuya; Wu, Jun; Chen, Linling; Lu, Jianming; Wang, Xiaochen; Liu, Xiyong; Zhou, Bingsen; Yen, Yun.

In: Molecular Cancer, Vol. 8, 11, 28.02.2009.

Research output: Contribution to journalArticle

Zhang, Keqiang ; Hu, Shuya ; Wu, Jun ; Chen, Linling ; Lu, Jianming ; Wang, Xiaochen ; Liu, Xiyong ; Zhou, Bingsen ; Yen, Yun. / Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo : Implication of RRM2 in angiogenesis. In: Molecular Cancer. 2009 ; Vol. 8.
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abstract = "Background: In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2. Results: We examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts. Conclusion: These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.",
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AU - Zhang, Keqiang

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AU - Wu, Jun

AU - Chen, Linling

AU - Lu, Jianming

AU - Wang, Xiaochen

AU - Liu, Xiyong

AU - Zhou, Bingsen

AU - Yen, Yun

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