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Angiogenesis in breast cancer: The role of transforming growth factor ? and CD105
- Source :
- Microscopy Research and Technique. 52:437-449
- Publication Year :
- 2001
- Publisher :
- Wiley, 2001.
-
Abstract
- The progression of breast cancer depends on the establishment of a neovasculature, by a process called angiogenesis. Angiogenesis is an invasive cellular event that requires the co-ordination of numerous molecules including growth factors and their receptors, extracellular proteins, adhesion molecules, and proteolytic enzymes. TGFbeta has emerged to be a major modulator of angiogenesis by regulating endothelial cell proliferation, migration, extracellular matrix (ECM) metabolism, and the expression of adhesion molecules. It is a potent growth inhibitor of normal mammary epithelial cells and a number of breast cancer cell lines. It seems that TGFbeta exerts pleiotropic effects in the oncogenesis of breast cancers in a contextual manner, i.e., it suppresses tumourigenesis at an early stage by direct inhibition of angiogenesis and tumour cell growth. However, over-production of TGFbeta by an advanced tumour may accelerate disease progression through indirect stimulation of angiogenesis and immune suppression. The cell membrane antigen CD105 (endoglin) binds TGFbeta1 and TGFbeta3 and is preferentially expressed in angiogenic vascular endothelial cells. The reduction of CD105 levels in HUVEC leads to in vitro angiogenesis inhibition and massive cell mortality in the presence of TGFbeta1. CD105 null mice die in utero with impaired vasculature, indicating the pivotal role of CD105 in vascular development. The administration of an immunotoxin-conjugate, mab to CD105, induces long-term and complete regression of breast cancer growth in SCID mice. Therefore, CD105 is a promising vascular target for antiangiogenic therapy.
- Subjects :
- medicine.medical_specialty
Histology
biology
Cell growth
Cell adhesion molecule
Angiogenesis
Transforming growth factor beta
Endoglin
Extracellular matrix
Endothelial stem cell
Medical Laboratory Technology
Endocrinology
Internal medicine
medicine
biology.protein
Cancer research
Anatomy
Instrumentation
Transforming growth factor
Subjects
Details
- ISSN :
- 10970029 and 1059910X
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Microscopy Research and Technique
- Accession number :
- edsair.doi...........5ac9875eee39d8f722b0ccd0983db617