Growth and angiogenesis of human breast cancer in a nude mouse tumour model is reduced by NK4, a HGF/SF antagonist
Abstract
Hepatocyte growth factor/scatter factor (HGF/SF) is a cytokine primarily produced by stromal fibroblasts and is a known angiogenic and invasion-inducing factor. It is increased in patients with breast cancer. This study examined the effect of NK4, a newly described HGF/SF antagonist, on HGF/SF-promoted growth of a human breast cancer. Both in vitro (invasion and migration assays) and in vivo (murine tumour model) methods were used to ascertain the effect of NK4 on HGF/SF from two sources: human fibroblast-derived HGF/SF and recombinant HGF/SF. In the in vitro invasion assay and migration assay, both HGF/SF and human fibroblasts, which secrete bioactive HGF/SF, increased the invasiveness and migration of the breast cancer cells (MDA MB 231). NK4 significantly reduced this invasiveness and motility. In the animal model, tumour volume and weight was significantly reduced with addition of NK4. It also suppressed HGF/SF-induced growth and markedly retarded tumour growth induced by fibroblasts (MRC5), secreting bioactive HGF/SF. Tumour angiogenesis was assessed by immunohistochemical staining of primary tissue sections using VE-cadherin (an endothelial cell specific cell-cell adhesion molecule). Again, NK4 reduced the effects of both HGF/SF and fibroblasts. We conclude that NK4 has a significant effect on the growth of human breast tumours in nude mice, particularly when stimulated by HGF/SF or fibroblasts. This may occur by decreasing angiogenesis. This gives a clear indication of the therapeutic worth of NK4.
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Bone marrow-derived MSC and adipose-derived stem/stromal cells can secrete a combination of anti-apoptotic and angiogenic factors, including HGF, SDF-1/CXCL12, CD106 and VEGF, which can promote tumor growth, local angiogenesis and metastasis.
“BM-MSC and ASC can also secrete a combination of anti-apoptotic and angiogenic factors [121], including HGF, SDF-1/CXCL12, CD106 (sVCAM) and VEGF which can promote tumor growth, local angiogenesis and metastasis [42, 84, 122–127].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [42]
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- Authors
- Martin, T. A., Parr, C., Davies, G., Watkins, G., Lane, J., Matsumoto, K., Nakamura, T., Mansel, R. E., & Jiang, W. G.
- Affiliations
- Cardiff University (GB)
- University of Wales (GB)
- Osaka University Hospital (JP)
- Corresponding author
- Martin, T. A.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-05-09
- Volume
- 24
- Issue
- 8
- Pages
- 1317-1323
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2111279109
- Cited by
- 79
- References
- 51
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 2 · 2020: 2 · 2019: 3 · 2017: 3 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 2
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK
- Breast Cancer Campaign
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- NK4, hepatocyte growth factor, breast cancer, tumor angiogenesis, tumor growth, tumor invasion, cell migration, MDA-MB-231 cells, MRC-5 fibroblasts, VE-cadherin, angiogenesis inhibitors
- MeSH terms
- Animals, Breast Neoplasms, Cell Adhesion, Cell Division, Cell Movement, Cytoskeletal Proteins, Disease Models, Animal, Female, Fibroblasts, Humans, Mice, Nude, Mitogens, Neoplasm Invasiveness, Neovascularization, Pathologic, Phosphoproteins, Phosphorylation, Tumor Cells, Cultured, Tyrosine, Blotting, Western, Gene Expression Regulation, Neoplastic, Survival Rate, Hepatocyte Growth Factor, Proto-Oncogene Proteins c-met, Mice, Paxillin
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