Endothelial progenitor cells do not contribute to tumor endothelium in primary and metastatic tumors
| Autor: | Anke Wickersheim, Mark Kerber, Lourdes Sanchez de Miguel, Karl H. Plate, Marcia Machein |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Cancer Research Pathology medicine.medical_specialty Lung Neoplasms Endothelium Angiogenesis Melanoma Experimental Biology Metastasis Immunoenzyme Techniques Carcinoma Lewis Lung Mice chemistry.chemical_compound Bone Marrow medicine Animals Humans Progenitor cell Bone Marrow Transplantation Stem Cells Prostatic Neoplasms Lewis lung carcinoma medicine.disease Mice Inbred C57BL Endothelial stem cell Vascular endothelial growth factor medicine.anatomical_structure Oncology chemistry Tumor progression cardiovascular system Endothelium Vascular |
| Zdroj: | International Journal of Cancer. 125:1771-1777 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Despite extensive research, the contribution of bone-marrow-derived endothelial progenitor cells (BM-EPC) to tumor angiogenesis remains controversial. In previous publications, the extent of incorporation of BM-EPCs into the endothelial cell (EC) layer in different tumor models has been reported as significant in some studies but undetectable in others. Here, we studied the differentiation of BM-EPCs and its contribution to tumor vessels in experimental and spontaneous lung metastasis (B16 melanoma and prostate carcinoma), in an autochthonous transgenic model of prostate tumorigenesis, in orthotopically implanted lung tumors [Lewis lung carcinoma (LLC)], in heterotopic subcutaneous models (LLC and C1 prostate carcinoma) growing in green fluorescent protein (GFP)-expressing bone marrow (BM) chimeras. Immunofluorescence was performed with a set of endothelial and hematopoietic markers and confocal microscopy was used to generate 3D reconstruction images. By performing rigorously conducted morphological studies, we found no evidence of BM-EPCs differentiation into tumor endothelium independently of tumor type, grade and organ site in primary and metastatic tumors. The vast majority of GFP(+) cells were trafficking leucocytes or periendothelial myeloid cells. To explore the possibility that local overexpression of vascular endothelial growth factor (VEGF) might increase the numbers of incorporated BM-EPCs, we analyzed tumors genetically manipulated to overexpress VEGF(164). Local VEGF production induces a massive infiltration of bone-marrow-derived cells, but did not lead to vessel wall integration of these cells. Collectively, these findings suggest that during tumor progression vascularization occurs primarily via classical tumor angiogenesis (e.g., sprouting of pre-existing ECs), whereas BM-EPCs do not incorporate into the vessel wall to any significant extent. |
| Databáze: | OpenAIRE |
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