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A novel gene expression profile in lymphatics associated with tumor growth and nodal metastasis
- Source :
- Cancer research. 68(18)
- Publication Year :
- 2008
-
Abstract
- Invasion of lymphatic vessels is a key step in the metastasis of primary tumors to draining lymph nodes. Although the process is enhanced by tumor lymphangiogenesis, it is unclear whether this is a consequence of increased lymphatic vessel number, altered lymphatic vessel properties, or both. Here we have addressed the question by comparing the RNA profiles of primary lymphatic endothelial cells (LEC) isolated from the vasculature of normal tissue and from highly metastatic T-241/vascular endothelial growth factor (VEGF)-C fibrosarcomas implanted in C57BL/6 mice. Our findings reveal significant differences in expression of some 792 genes (i.e., ≥2-fold up- or down-regulated, P ≤ 0.05) that code for a variety of proteins including components of endothelial junctions, subendothelial matrix, and vessel growth/patterning. The tumor LEC profile, validated by immunohistochemical staining, is distinct from that of normal, inflammatory cytokine, or mitogen-activated LEC, characterized by elevated expression of such functionally significant molecules as the tight junction regulatory protein endothelial specific adhesion molecule (ESAM), the transforming growth factor-β coreceptor Endoglin (CD105), the angiogenesis-associated leptin receptor, and the immunoinhibitory receptor CD200, and reduced expression of subendothelial matrix proteins including collagens, fibrillin, and biglycan. Moreover, we show similar induction of ESAM, Endoglin, and leptin receptor within tumor lymphatics in a series of human head and neck and colorectal carcinomas, and uncover a dramatic correlation between ESAM expression and nodal metastasis that identifies this marker as a possible prognostic indicator. These findings reveal a remarkable degree of phenotypic plasticity in cancer lymphatics and provide new insight into the processes of lymphatic invasion and lymph node metastasis. [Cancer Res 2008;68(18):7293–303]
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Junctional Adhesion Molecules
Lymphovascular invasion
government.form_of_government
Fibrosarcoma
Vascular Endothelial Growth Factor C
Cell Growth Processes
Biology
Metastasis
chemistry.chemical_compound
Mice
Transforming Growth Factor beta
Neoplasms
Lymphatic vessel
medicine
Animals
Humans
Oligonucleotide Array Sequence Analysis
Leptin receptor
Neovascularization, Pathologic
Gene Expression Profiling
Endoglin
Intracellular Signaling Peptides and Proteins
Endothelial Cells
medicine.disease
Vascular endothelial growth factor
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Lymphatic Endothelium
Lymphatic system
medicine.anatomical_structure
Oncology
chemistry
Lymphatic Metastasis
government
Receptors, Leptin
Lymph Nodes
Cell Adhesion Molecules
Subjects
Details
- Language :
- English
- ISSN :
- 15387445 and 00085472
- Volume :
- 68
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....5fcbe1b29bbd0e19cbcbe4c508002331