In vivo 'MRI phenotyping' reveals changes in extracellular matrix transport and vascularization that mediate VEGF-driven increase in breast cancer metastasis
| Autor: | Venu Raman, Stephen McNutt, Zaver M. Bhujwalla, Arvind P. Pathak, Flonne Wildes, Tariq Shah |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pathology Angiogenesis lcsh:Medicine Vascular permeability Cardiovascular Metastasis Diagnostic Radiology Extracellular matrix Mice 0302 clinical medicine Molecular Cell Biology Basic Cancer Research Tumor Microenvironment skin and connective tissue diseases lcsh:Science 0303 health sciences Multidisciplinary Neovascularization Pathologic Obstetrics and Gynecology Magnetic Resonance Imaging Extracellular Matrix 3. Good health Vascular endothelial growth factor A Phenotype Oncology Lymphatic Metastasis 030220 oncology & carcinogenesis MCF-7 Cells Medicine Female Cellular Types Radiology Research Article medicine.medical_specialty Mice Nude Breast Neoplasms Biology 03 medical and health sciences Breast cancer Vascular Biology In vivo Breast Cancer Cancer Detection and Diagnosis medicine Animals Humans Neoplasm Invasiveness 030304 developmental biology Tumor microenvironment lcsh:R Endothelial Cells Biological Transport medicine.disease Extracellular Matrix Composition Cancer research lcsh:Q Neoplasm Transplantation |
| Zdroj: | PLoS ONE, Vol 8, Iss 5, p e63146 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Purpose To gain new insights into the relationship between angiogenic factors in breast cancer and their effect on extracellular matrix (ECM) remodeling and metastasis, we characterized and validated the “metastatic signature” of human breast cancer cell lines engineered to overexpress VEGF in terms of in vivo MRI-derived angiogenesis and ECM transport parameters. Methodology MRI was used to evaluate the effects of overexpressing VEGF-A (VEGF165) on tumor angiogenesis and ECM remodeling in vivo, for two differentially metastatic human breast cancer cell lines: MCF-7 and MDA-MB-231. Principal Findings Overexpression of VEGF elevated vascular volume in both MCF-7-VEGF and MDA-MB-231-VEGF tumors relative to their wild-type counterparts, but vascular permeability was elevated only in MCF-7-VEGF tumors. A significant increase in the volume of extravascular fluid drained as well as the number of ECM drainage voxels was detected in MCF-7-VEGF tumors relative to MCF-7 tumors, but not in MDA-MB-231-VEGF versus MDA-MB-231 tumors. The angiogenic effects of VEGF overexpression in both MCF-7-VEGF and MDA-MB-231-VEGF tumors were validated histologically. MCF-7-VEGF tumors exhibited enhanced invasion and a greater fraction of cancer positive lungs and lymph nodes relative to MCF-7 tumors. Conclusions and Significance In vivo MRI and histological data demonstrate that VEGF overexpression results in the progression of noninvasive MCF-7 and invasive MDA-MB-321 tumors to a more angiogenic phenotype. However, VEGF overexpression significantly altered ECM integrity only in MCF-7 tumors, causing them to progress to an invasive and metastatic phenotype. This study for the first time demonstrates the concurrent effects of VEGF overexpression and ECM remodeling on metastasis in vivo. Collectively, these findings demonstrate that in vivo MRI can non-invasively monitor changes in the tumor microenvironment that can potentially predict a cancer’s ability to metastasize. |
| Databáze: | OpenAIRE |
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