Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs

Ming Hsien Chien, Liang Ming Lee, Michael Hsiao, Lin Hung Wei, Chih Hau Chen, Tsung Ching Lai, Kuo Tai Hua, Min Wei Chen, Chung Ming Sun, Min Liang Kuo

研究成果: 雜誌貢獻 › 文章

6 引文 (Scopus)

摘要

Angiogenesis and lymphangiogenesis are considered to play key roles in tumor metastasis. Targeting receptor tyrosine kinases essentially involved in the angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis. However, the optimal multikinase inhibitor for metastasis suppression has yet to be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A), a multikinase inhibitor of vascular endothelial growth factor receptors (VEGFRs)/fibroblast growth factor receptors (FGFRs), on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of the highly invasive breast cancer cell line 4T1-Luc+. We investigated the biologic effect of 194-A on various invasive breast cancer cell lines as well as endothelial and lymphatic endothelial cells. Intriguingly, we found that 194-A drastically reduced the formation of lung, liver, and lymph node metastasis of 4T1-Luc+ and decreased primary tumor growth. This was associated with significant reductions in intratumoral lymphatic vessel length (LVL) and microvessel density (MVD). 194-A blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial cells. Moreover, 194-A significantly inhibited the invasive capacity induced by VEGF-C or FGF-2 in vitro in both 4T1 and MDA-MB231 cells. In conclusion, these experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs kinases may be a promising strategy to prevent breast cancer metastasis.
原文英語
文章編號718380
期刊Evidence-based Complementary and Alternative Medicine
卷2013
DOIs
出版狀態已發佈 - 2013

指紋

Fibroblast Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
Lymphangiogenesis
Breast Neoplasms
Neoplasm Metastasis
Endothelial Cells
Vascular Endothelial Growth Factor C
Cell Line
Neoplasms
Lymphatic Vessels
Receptor Protein-Tyrosine Kinases
Fibroblast Growth Factor 2
Microvessels
Heterografts
Adipose Tissue
Breast
Phosphotransferases
Lymph Nodes
In Vitro Techniques
Lung

ASJC Scopus subject areas

  • Complementary and alternative medicine

引用此文

Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs. / Chien, Ming Hsien; Lee, Liang Ming; Hsiao, Michael; Wei, Lin Hung; Chen, Chih Hau; Lai, Tsung Ching; Hua, Kuo Tai; Chen, Min Wei; Sun, Chung Ming; Kuo, Min Liang.

於: Evidence-based Complementary and Alternative Medicine, 卷 2013, 718380, 2013.

研究成果: 雜誌貢獻 › 文章

Chien, MH, Lee, LM, Hsiao, M, Wei, LH, Chen, CH, Lai, TC, Hua, KT, Chen, MW, Sun, CM & Kuo, ML 2013, 'Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs', Evidence-based Complementary and Alternative Medicine, 卷 2013, 718380. https://doi.org/10.1155/2013/718380
Chien MH, Lee LM, Hsiao M, Wei LH, Chen CH, Lai TC 等. Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs. Evidence-based Complementary and Alternative Medicine. 2013;2013. 718380. https://doi.org/10.1155/2013/718380
Chien, Ming Hsien ; Lee, Liang Ming ; Hsiao, Michael ; Wei, Lin Hung ; Chen, Chih Hau ; Lai, Tsung Ching ; Hua, Kuo Tai ; Chen, Min Wei ; Sun, Chung Ming ; Kuo, Min Liang. / Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs. 於: Evidence-based Complementary and Alternative Medicine. 2013 ; 卷 2013.
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abstract = "Angiogenesis and lymphangiogenesis are considered to play key roles in tumor metastasis. Targeting receptor tyrosine kinases essentially involved in the angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis. However, the optimal multikinase inhibitor for metastasis suppression has yet to be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A), a multikinase inhibitor of vascular endothelial growth factor receptors (VEGFRs)/fibroblast growth factor receptors (FGFRs), on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of the highly invasive breast cancer cell line 4T1-Luc+. We investigated the biologic effect of 194-A on various invasive breast cancer cell lines as well as endothelial and lymphatic endothelial cells. Intriguingly, we found that 194-A drastically reduced the formation of lung, liver, and lymph node metastasis of 4T1-Luc+ and decreased primary tumor growth. This was associated with significant reductions in intratumoral lymphatic vessel length (LVL) and microvessel density (MVD). 194-A blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial cells. Moreover, 194-A significantly inhibited the invasive capacity induced by VEGF-C or FGF-2 in vitro in both 4T1 and MDA-MB231 cells. In conclusion, these experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs kinases may be a promising strategy to prevent breast cancer metastasis.",
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AU - Chen, Chih Hau

AU - Lai, Tsung Ching

AU - Hua, Kuo Tai

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