Abstract
We introduce two methods, both of which are based on cellular-extracellular matrix interaction, which will facilitate the study of human microvascular endothelial cells. One method describes the means to obtain a G1 population baseline in human microvasclular endothelial cells. Because of the contribution of the extracellular matrix in endothelial cell growth, synchronization in G1 was possible only after the incorporation of angiostatic levels of heparin and hydrocortisone into the extracellular matrix. In the second method, we demonstrate that selective perturbation of human microvascular endothelial cell-extracellular matrix interactions results in the induction of a transitional growth state, between proliferative and differentiated growth states, in human microvascular endothelial cells. In the functional, microtubule formation assays, transitional growth state endothelial cells display rates that are indermediate between those obtained from differentiated and proliferative endothelial cells. Our results demonstrate the importance of the human microvascular endothelial cell-extracellular matrix interaction in the determination of cellular growth state. Our findings also imply that responsiveness of microvascular endothelial cells to their cellular-extracellular matrix environs is highest during the differentiated growth state.
Similar content being viewed by others
References
Albelda SM, Buck CA (1990) Integrins and other cell adhesion molecules. FASEB J 4:2868–2880
Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1989) Cell growth and division. In: Adams R (ed) Molecular biology of the cell. Garlan, New York, pp 611–671
Basson CT, Kocher O, Basson MD, Asis A, Madri JA (1992) Differential modulation of vascular cell integrin and extracellular matrix expression in vitro by TGF-B1 correlates with reciprocal effects on cell migration. J Cell Physiol 153:118–128
Bauer J, Margolis M, Schreiner C, Edgell CG, Azizkhan J, Lazarowski E, Juliano RL (1992) In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression. G-proteins, and integrins. J Cell Physiol 153:437–449
Beck DW, Olson JJ, Linhardt RJ (1986) Effect of heparin, heparin fragments, and corticosteroids on cerebral endothelial cell growth in vitro and in vivo. J Neuropathol Exp Neurol 45:503–511
Belloni PN, Tressler RJ (1990) Microvascular endothelial cell heterogeneity: interactions with leukocytes and tumor cells. Cancer Metabol Rev 8:353–389
Dike LA, Farmer SR (1988) Cell adhesion induces expression of growth-associated genes in suspension-arrested fibroblasts. Proc Natl Acad Sci USA 85:6792–6796
Fajardo LF (1989) The complexity of endothelial cells. Am J Clin Pathol 92:241–250
Folkman J (1992) The role of angiogenesis in tumor growth. Semin Cancer Biol 3:65–71
Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934
Folkman J, Langer R, Linhardt RJ, Haudenschild C, Taylor S (1983) Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone. Science 221:719–725
Heino J, Massague J (1989) Transforming growth factor beta switches the pattern of integrins expressed in MG-63 human osteosarcoma cells and causes a selective loss of adhesion to lanimin. J Biol Chem 264:21806–21811
Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554
Kramer RH, Cheng YF, Clyman R (1990) Human microvascular endothelial cells use B1 and B3 integrin receptor complexes to attach to laminin. J Cell Biol 111:1233–1243
Ingber DE (1990) Fibronectin controls capillary endothelial cell growth by modulating cell shape. Proc Natl Acad Sci USA 87:3579–3583
Ingber DE (1992) Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy
Ingber DE, Folkman J (1989a) Mechanochemical switching between growth and differentiation during fibroblast factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol 109:317–330
Ingber DE, Folkman J (1989b) Tension and compression as basic determinants of cell form and function: utilization of a cellular tensegrity mechanism. In: Stein WD, Bronner F (eds) Cell shape: determinants, regulation and regulatory roles. Academic Press San Diego, pp 3–31
Klagsbrun M, D'Amore PA (1991) Regulators of angiogenesis. Annu Rev Physiol 53:217–239
Larsen JK, Munch-Petersen B, Christensen J, Jorgensen R (1986) Flow cytometric discrimination of M, as well as G1, S, and G2 phase nuclei with mithramycin, propidium iodide, and ethidium bromide after fixation with formaldehyde. Cytometry 7:54–63
Maciag T (1990) Molecular and cellular mechanisms of angiogenesis. (Important advances in oncology: molecular and cellular mechanisms of angiogenesis). Lippincott, Philadelphia, pp 85–98
Maciag T, Weinstein R (1984) Preparation of endothelial cell growth factor. In: Barnes DW, Sirbasky DA, Sate GH (eds) Cell culture methods for molecular and cell biology, vol 1. Liss, New York, pp 195–205
Mallery SR, Laufman HB, Solt CW, Stephens RE (1991) Association of cellular thiol redox status with mitogen-induced calcium mobilization and cell cycle progression in human fibroblasts. J Cell Biochem 45:82–92
Mallery SR, Lantry LE, Laufman HB, Stephens RE, Brierley GP (1993) Modulation of human microvascular endothelial cell bioenergetic status and glutathione levels during proliferative and differentiated growth. J Cell Biochem 53:360–372
Matthews CK, Holde KE van (1990) Metabolism of nitrogenous compounds: amino acids. In: Bowen D, Weisberg S (eds) Biochemistry. Benjamin Cummings Publishing, Redwood City, Calif, pp 610–611, 712–714
Murray AW, Kirschner MW (1989) Dommoes and clocks: the union of two views of the cell cycle. Science 246:614–621
Pardee AB (1989) G1 events and regulation of cell proliferation. Science 246:603–608
Pollack A (1990) Flow cytometric cell-kinetic analysis by simultaneously staining nuclei with propidium iodide and fluorescein isothiocyanate. Methods Cell Biol 33:315–323
Ruoslahti E (1989) Proteoglycans in cell regulation. J Biol Chem 264:13369–13372
Springer TA (1990) Adhesion receptors of the immune system. Nature 346:425–434
Tooker JE (1989) Microcirculation and diabetes. Br Med Bull 45:206–223
Van Kuppevelt TH, Languino LR, Gailit JO, Suzuki S, Ruoslahti E (1989) An alternative cytoplasmic domain of the integrin B1 subunit. Proc Natl Acad Sci USA 86:5415–5418
Voyta JC, Via DP, Butterfield CE, Zetter BR (1984) Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol 99:2034–2040
Wilke MS, Hsu BM, Scott RE (1988) Two subtypes of reversible cell cycle restriction points exist in cultured normal keratinocyte progenitor cells. Lab Invest 58:660–666
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mallery, S.R., Lantry, L.E., Toms, M.C. et al. Human microvascular endothelial cell-extracellular matrix interaction in cellular growth state determination. Cell Tissue Res 279, 37–45 (1995). https://doi.org/10.1007/BF00300689
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00300689