Abstract
Solid tumors require new blood vessels for growth and metastasis, yet the biology of tumor-specific endothelial cells is poorly understood. We have isolated tumor endothelial cells from mice that spontaneously develop prostate tumors. Clonal populations of tumor endothelial cells expressed hematopoietic and mesenchymal stem cell markers and differentiated to form cartilage- and bone-like tissues. Chondrogenic differentiation was accompanied by an upregulation of cartilage-specific col2a1 and sox9, whereas osteocalcin and the metastasis marker osteopontin were upregulated during osteogenic differentiation. In human and mouse prostate tumors, ectopic vascular calcification was predominately luminal and colocalized with the endothelial marker CD31. Thus, prostate tumor endothelial cells are atypically multipotent and can undergo a mesenchymal-like transition.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / metabolism
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Animals
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Antigens, Surface / genetics
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Antigens, Surface / metabolism
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Calcinosis / genetics
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Calcinosis / metabolism
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Calcinosis / pathology*
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Cell Transdifferentiation*
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Chondrocytes / metabolism
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Chondrocytes / pathology
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Collagen Type II / metabolism
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Endothelial Cells / metabolism
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Endothelial Cells / pathology
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Endothelial Cells / transplantation
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology*
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Gene Expression
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High Mobility Group Proteins / metabolism
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Humans
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Male
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Mesenchymal Stem Cells / metabolism
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Mesenchymal Stem Cells / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Osteocalcin / metabolism
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Osteocytes / metabolism
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Osteocytes / pathology
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Osteopontin / metabolism
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Platelet Endothelial Cell Adhesion Molecule-1 / genetics
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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SOX9 Transcription Factor
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Thy-1 Antigens / metabolism
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Tissue Array Analysis
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Transcription Factors / metabolism
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Tumor Cells, Cultured
Substances
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Antigens, Surface
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Col2a1 protein, mouse
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Collagen Type II
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High Mobility Group Proteins
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Platelet Endothelial Cell Adhesion Molecule-1
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SOX9 Transcription Factor
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SOX9 protein, human
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Sox9 protein, mouse
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Spp1 protein, mouse
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Thy-1 Antigens
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Transcription Factors
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Osteocalcin
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Osteopontin
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Alkaline Phosphatase