The objectives of this research are: (1) to purify a molecule produced by a human hepatoma cell (HHC) line which is able to induce the production of latent collagenase and plasminogen activator (PA) in capillary endothelial cells; and (2) to relate the ability of this molecule to induce latent collagenase and PA in endothelial cells in vitro to its ability to cause neovascularization in vivo. We have determined that human hepatoma cells produce a molecule which stimulates by 10- to 50-fold the production of latent collagenase and PA by cultured, primary bovine capillary endothelial (BCE) cells. We hypothesize that the active molecule produced by the hepatoma cells is a physiological inducer of neovascularization. We believe, that during neovascularization in vivo, this molecule stimulates the production of latent collagenase and PA by endothelial cells, thereby inducing two enzymes required for the penetration of new capillaries into surrounding tissues. To test this hypothesis, we will do the following: (1) purify and characterize the molecule(s) produced by HHC which induces latent collagenase and and PA in BCE cells; (2) assay the ability of this molecule to induce angiogenesis in vivo; and (3) establish cultures of human capillary endothelial cells to determine whether the effects of the HHC factor on human cells are comparable to those on BCE cells. (L)
| Deryugina, Elena I; Zajac, Ewa; Zilberberg, Lior et al. (2018) LTBP3 promotes early metastatic events during cancer cell dissemination. Oncogene 37:1815-1829 |
| Rifkin, Daniel B; Rifkin, William J; Zilberberg, Lior (2018) LTBPs in biology and medicine: LTBP diseases. Matrix Biol 71-72:90-99 |
| Morkmued, Supawich; Hemmerle, Joseph; Mathieu, Eric et al. (2017) Enamel and dental anomalies in latent-transforming growth factor beta-binding protein 3 mutant mice. Eur J Oral Sci 125:8-17 |
| Recouvreux, M Victoria; Camilletti, M Andrea; Rifkin, Daniel B et al. (2016) The pituitary TGF?1 system as a novel target for the treatment of resistant prolactinomas. J Endocrinol 228:R73-83 |
| Robertson, Ian B; Rifkin, Daniel B (2016) Regulation of the Bioavailability of TGF-? and TGF-?-Related Proteins. Cold Spring Harb Perspect Biol 8: |
| Zilberberg, Lior; Phoon, Colin K L; Robertson, Ian et al. (2015) Genetic analysis of the contribution of LTBP-3 to thoracic aneurysm in Marfan syndrome. Proc Natl Acad Sci U S A 112:14012-7 |
| Robertson, Ian B; Horiguchi, Masahito; Zilberberg, Lior et al. (2015) Latent TGF-?-binding proteins. Matrix Biol 47:44-53 |
| Horiguchi, Masahito; Todorovic, Vesna; Hadjiolova, Krassimira et al. (2015) Abrogation of both short and long forms of latent transforming growth factor-? binding protein-1 causes defective cardiovascular development and is perinatally lethal. Matrix Biol 43:61-70 |
| Dabovic, Branka; Robertson, Ian B; Zilberberg, Lior et al. (2015) Function of latent TGF? binding protein 4 and fibulin 5 in elastogenesis and lung development. J Cell Physiol 230:226-36 |
| Rognoni, Emanuel; Widmaier, Moritz; Jakobson, Madis et al. (2014) Kindlin-1 controls Wnt and TGF-? availability to regulate cutaneous stem cell proliferation. Nat Med 20:350-9 |
Showing the most recent 10 out of 121 publications
