ArticleClinical & experimental metastasis2007
Differential expression of hypoxia and (lymph)angiogenesis-related genes at different metastatic sites in breast cancer.
Article in Clinical & experimental metastasis, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
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- The type of metastasis is a prognostic factor in disseminated cervical cancer.Journal of gynecologic oncology · 2010Article
- Mechanisms of bone metastases of breast cancer.Endocrine-related cancer · 2009Review
- Epigenetic contributions to cancer metastasis.Clinical & experimental metastasis · 2009Article
- Metastasis: a therapeutic target for cancer.Nature clinical practice. Oncology · 2008Review
- Concerted transcriptional regulation by BRCA1 and COBRA1 in breast cancer cells.International journal of biological sciences · 2007Article
- Lymphatic metastasis in breast cancer: importance and new insights into cellular and molecular mechanisms.Clinical & experimental metastasis · 2007Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionBreast cancer can metastasize via lymphatic and hematogenous pathways. Hypoxia and (lymph)angiogenesis are closely related processes that play a pivotal role in the tumor progression and metastasis. The aim of this study was to compare expression of hypoxia and (lymph)angiogenesis-related genes between primary breast tumors and metastases in different tissues. MATERIALS AND
methodsA gene list of 269 hypoxia and (lymph)angiogenesis-related genes was composed and validated using Onto-Express, Pathway-express and Ingenuity software. The expression of these genes was compared in microarray data of 62 samples of primary tumors and metastases of 31 patients with breast cancer retrieved from Gene Expression Omnibus. Similarity between samples was investigated using unsupervised hierarchical clustering analysis, principal component analysis and permutation testing. Differential gene expression between primary tumors and metastases and between metastases from different organs was analyzed using Kruskall-Wallis and Mann-Whitney statistics.
resultsUnsupervised hierarchical cluster analysis demonstrated that hypoxia and (lymph)angiogenesis-related gene expression was more similar between samples from the same patient, than between samples from the same organ. Principal component analysis indicated that 22.7% and 7.0% of the total variation in the gene list was respectively patient and organ related. When differences in gene expression were studied between different organs, liver metastases seemed to differ most from the other secondary sites. Some of the best characterized molecules differentially expressed were VEGFA, PDGFRB, FGF4, TIMP1, TGFB-R1 and collagen 18A1 (precursor of endostatin). To confirm the results of these experiments at the protein level, immunohistochemical experiments were performed with antibodies for VEGFA and MMP-2.
conclusionsOur results suggest that hypoxia and (lymph)angiogenesis-related gene expression is more dependent on the characteristics of the primary tumor than on the characteristics of the organs that bear the metastasis. However, when different organs are compared, the expression in liver metastases differs most from other metastatic sites and primary tumors, possibly due to organ-specific angiogenic and lymphangiogenic responses to metastasis-related hypoxia.
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