Apolipoprotein(a), a link between atherosclerosis and tumor angiogenesis.
Lipoprotein (a) [Lp(a)] is a LDL-like particle with one apolipoprotein(a) [apo(a)] covalently bound to apolipoprotein B, the structural protein of Low Density Lipoprotein (LDL). Lewis Lung Carcinoma (LL/2) cells exhibited delayed growth and reduced angiogenesis in apo(a) transgenic mice, expressing a recombinant apo(a) [r-apo(a)] with 18 kringle 4 repeats. The mean microvessel density of subcutaneous LL/2 tumors from apo(a) transgenic mice was significantly lower than that of tumors from control wild type mice. CHO cells secreting a truncated apo(a) protein with only six kringle 4 repeats did not exhibit delayed tumor growth nor did it impair angiogenesis. These data point to an unappreciated role of human apo(a) in angiogenesis and cancer biology. As angiogenesis is necessary for reendothelialization following vascular injury, suppression of angiogenesis by apo(a) may also contribute to the atherogenicity of apo(a). The differences between the truncated apo(a) and r-apo(a) are consistent with the higher atherogenicity of higher molecular weight isoforms.
Trieu
V N
VN
Department of Cardiovascular Biology, Department of Molecular Epidemiology, Hughes Institute, 2665 Long Lake Road, St. Paul, Minnesota, 55113, USA.
Uckun
F M
FM
D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000473:pathology*; D016466:CHO Cells; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000473:pathology; D002455:Cell Division; D006224:Cricetinae; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D018082:Kringles / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D001054:Apolipoproteins A; D011994:Recombinant Proteins