The role of basement membrane in angiogenesis and tumor growth.
Expansion of the tumor-cell mass is dependent on both the degree of tumor vascularization and the rate of angiogenesis. Blood vessel growth is controlled, in part, by the matrix surrounding it, in particular, the basement membrane underlying the endothelium. Here we illustrate that laminin, a major component of basement membrane, has several biologically active sites that can bind to endothelial and tumor cells, and have the ability to regulate angiogenesis and tumor growth. We show that synthetic peptides at two sites in the laminin B1 chain (the RGD and YIGSR sequences) inhibit angiogenesis, whereas a third site in the A chain, designated SIK-VAV, stimulates vessel and tumor cell growth. By developing strategies that promote or inhibit the activities of these sites in laminin, we may obtain methods to inhibit angiogenesis and subsequent tumor growth.
Grant
D S
DS
Laboratory of Development Biology, National Institute of Dental Research, NIH, Bethesda, MD.
Kibbey
M C
MC
Kinsella
J L
JL
Cid
M C
MC
Kleinman
H K
HK
D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D007797:Laminin / Q000032:analysis / Q000502:physiology*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*
D007797:Laminin