期刊
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
卷 51, 期 11, 页码 1393-1410出版社
HISTOCHEMICAL SOC INC
DOI: 10.1177/002215540305101101
关键词
perlecan; heparan sulfate proteoglycan; tumor angiogenesis; vascular endothelial growth factor; fibroblast growth factor
类别
资金
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR036457] Funding Source: NIH RePORTER
- NIAMS NIH HHS [AR 36457] Funding Source: Medline
Perlecan is a major heparan sulfate proteoglycan (HSPG) of basement membranes (BMs) and connective tissues. The core protein of perlecan is divided into five domains based on sequence homology to other known proteins. Commonly, the N-terminal domain I of mammalian perlecan is substituted with three HS chains that can bind a number of matrix molecules, cytokines, and growth factors. Perlecan is essential for metazoan life, as shown by genetic manipulations of nematodes, insects, and mice. There are also known human mutations that can be lethal. In vertebrates, new functions of perlecan emerged with the acquisition of a closed vascular system and skeletal connective tissues. Many of perlecan's functions may be related to the binding and presentation of growth factors to high-affinity tyrosine kinase (TK) receptors. Data are accumulating, as discussed here, that similar growth factor-mediated processes may have unwanted promoting effects on tumor cell proliferation and tumor angiogenesis. Understanding of these attributes at the molecular level may offer opportunities for therapeutic intervention.
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