Article

Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.

Department of Surgery, Children's Hospital, Boston, Massachusetts.
Cell (Impact Factor: 33.12). 11/1994; 79(2):315-28.
Source: PubMed

ABSTRACT The phenomenon of inhibition of tumor growth by tumor mass has been repeatedly studied, but without elucidation of a satisfactory mechanism. In our animal model, a primary tumor inhibits its remote metastases. After tumor removal, metastases neovascularize and grow. When the primary tumor is present, metastatic growth is suppressed by a circulating angiogenesis inhibitor. Serum and urine from tumor-bearing mice, but not from controls, specifically inhibit endothelial cell proliferation. The activity copurifies with a 38 kDa plasminogen fragment that we have sequenced and named angiostatin. A corresponding fragment of human plasminogen has similar activity. Systemic administration of angiostatin, but not intact plasminogen, potently blocks neovascularization and growth of metastases. We here show that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin.

0 Followers
 · 
245 Views
  • The Journal of Cell Biology 03/2001; 152(6):35-36. · 9.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Paracrine effects can be exploited in cell-based therapies that secrete factors, such as chemokines and cytokines, and can recruit inflammatory cells to transplants. In this study, mouse adipose tissue-derived stromal cells (ASCs) and bone marrow-derived stromal cells (ST2 cells) were used to examine changes in paracrine interactions with inflammation cells. Green fluorescent protein positive (GFP(+)) bone marrow cells (BMCs) were injected into an irradiated mouse via femoral vein, and ASCs and ST2 cells were transplanted intradermally. Subsequently, an in vivo imaging system was used to observe behaviors of GFP(+) BMCs. To detect bone marrow-derived inflammatory cells which migrated in ASC and ST2 cell transplantation area, the sections were immunostained using antibodies against Gr1, CD11c, and F4/80, and secretory proteins were detected in culture medium using ELISA. Many bone marrow-derived inflammatory cells migrated to ASC and ST2 cell transplantation sites. Among these, neutrophils were detected during the early period and macrophages were predominantly detected at a later point in time. Many chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were secreted in abundance from ASCs, and the secretion increased by co-culturing with inflammatory cells, except for secretions of insulin-like growth factors -1, MMP-9 and MMP-13. Although secretions from ST2 cells were less than those from ASCs, co-culture with inflammatory cells increased these secretions to levels similar to those of ASCs. However, unlike ASCs, the ST2 cells did not secrete angiostatin, MMP-2, or MMP-3. Finally, ASCs secreted not only proinflammatory cytokines, angiogenic factors and MMPs but also anti-inflammatory cytokines, anti-angiogenesis factors, and TIMPs. The effects of cell-based therapies using ASCs and ST2 cells are depended on paracrine effects that are mediated by chemokines, cytokines, growth factors, MMPs, and TIMPs, which comprise responses to interactions between transplanted cells and inflammatory-cells. Moreover, paracrine effects of transplanted cells are influenced by inflammatory cells, and are moderated by a balance of secreted inhibitors.
    Stem Cell Research & Therapy 04/2015; 6(1):70. DOI:10.1186/s13287-015-0052-y · 4.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Artykuł otrzymano 25 sierpnia 2014 r. Artykuł zaakceptowano 5 listopada 2014 r. Słowa kluczowe: angiogeneza, śródbłonek, czynnik proangiogenny, czynnik antyan-giogenny, antyangiogenna terapia, nowo-twór, komórki macierzyste Wykaz skrótów: AML (ang. acute myelo-id leukemia) — ostra białaczka szpikowa; FGF (ang. fibroblast growth factor) — czyn-nik wzrostu fibroblastów; MMP (ang. matrix metalloproteinases) — metaloproteazy macierzy pozakomórkowej; PDGF (ang. platelet-derived growth factor) — płytkowy czynnik wzrostu; PF (ang. plasmaphere-sis) — plazmaferaza; PIGF (ang. placental growth factor) — łożyskowy czynnik wzro-stu; TGF-β (ang. Transforming Growth Factor beta) — transformujący czynnik wzrostu; VEGF (ang. vascular endothelial growth factor) — czynnik wzrostu śródbłonka naczy-niowego Podziękowania: Praca powstała podczas realizacji projektu badawczego finansowa-nego ze środków UE dla Programu Ope-racyjnego Innowacyjna Gospodarka " BIO-IMPLANT dla potrzeb leczenia ubytków tkanki kostnej u chorych onkologicznych " POIG.01.01.02-00-022/09-00. STRESZCZENIE A ngiogeneza to tworzenie nowych cienkościennych naczyń krwionośnych z już istnie-jących. Proces ten zachodzi poprzez tzw. pączkowanie (ang. sprouting angiogenesis) ko-mórek śródbłonka w okresie życia pozapłodowego. Proces ten ma zasadnicze znaczenie dla wielu zjawisk fizjologicznych i patologicznych, tj. wzrost nowotworów litych, rozwój chorób niedokrwiennych i przewlekłych zapaleń. Poznano różne mechanizmy tworzenia nowych naczyń krwionośnych i odkryto szereg czynników działających proangiogennie i antyangio-gennie. Zrozumienie funkcji tych czynników, przyczynia się do tworzenia nowych narzędzi terapii klinicznych w procesach patologicznych. W pracy przedstawiono charakterystykę procesów regulacji angiogenezy z uwzględnieniem najważniejszych czynników proangiogennych i ich inhibitorów. Opisuje wybrane mechani-zmy, na których opiera się działanie obecnie stosowanych leków antyangiogennych oraz jest przeglądem prowadzonych badań wykorzystujących czynniki w terapii antyangiogenicznej.
    Postepy biochemii 04/2015; 61(1):9.