Abstract
Tissue engineering, along with other modern celland tissue-based health care technologies, depends on successful regulation of cell function by molecular means, including pharmacological agents, materials, and genetics. This regulation is generally mediated by cell receptor/ligand interactions providing primary targets for molecular intervention. While regulatory ligands may often be exogenous in nature, in the categories of endocrine and paracrine hormone systems, they are being increasingly appreciated as crucial in local control of cell and tissue function. Improvements in design of health care technologies involving autocrine ligand interactions with cell receptors should benefit from increased qualitative and quantitative understanding of the kinetic and transport processes governing these interactions. In this symposium paper we offer a concise overview of our recent efforts combining molecular cell biology and engineering approaches to increase the understanding of how molecular and cellular parameters may be manipulated for improved control of cell and tissue function regulated by autocrine ligands.
Similar content being viewed by others
References
Akira, S., T. Hirano, T. Taga, and T. Kishimoto. Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF).FASEB J. 4:2860–2867, 1990.
Alcalay, M., D. Zingrilli, P. P. Pandolfi, L. Longo, A. Mencarelli, A. Glacomucciet al. Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid α locus.Proc. Natl. Acad. Sci. USA 88:1977–1981, 1991.
Baselga, J., and J. Mendelsohn. The epidermal growth factor receptor as a target for therapy in breast carcinoma.Breast Canc. Res. Treat. 29:127–138, 1994.
Bennett, N. T., and G. S. Schultz. Growth factors and wound healing, II: Role in normal and chronic wound healing.Am. J. Surg. 166:74–81, 1993.
Broder, S., ed. Molecular Foundations of Oncology. Baltimore: Williams & Wilkins, 1991.
Campion, S. R., D. R. Tadaki, and S. K. Niyogi. Evaluation of the role of electrostatic residues in human epidermal growth factor by site-directed mutagenesis and chemical modification.J. Cell Biochem. 50:35–42, 1992.
Cannon, W. B.. Organization for physiological homeostasis.Physiol. Rev. 9:399–431, 1929.
Castilla, A., J. Prieto, and N. Fausto. Transforming growth factors beta 1 and alpha in chronic liver disease.N. Engl. J. Med. 324:933–940, 1991.
Cima, L. G., D. Ingber, J. Vacanti, and R. Langer. Hepatocyte culture on biodegradable polymeric substrates.Biotech. Bioeng. 38:145–158, 1991.
Cima, L. G., and R. Langer. Engineering human tissue.Chem. Eng. Prog. June:46–54, 1993.
Cima, L. G., J. Vacanti, C. Vacanti, D. Ingber, D. Mooney, and R. Langer. Tissue engineering by cell transplantation using degradable polymer substrates.J. Biomech. Eng. 113:143–151, 1991.
Claret, E., J.-C. Renversez, X. Zheng, T. Bonnefoix, and J.-J. Sotto. Valid estimation of IL-2 secretion by PHA-stimulated T-cell clones absolutely requires the use of anti-CD25 monoclonal antibody to prevent IL-2 consumption.Immunol. Lett. 33:179–186, 1992.
Derynck, R. The physiology of transforming growth factor alpha.Adv. Canc. Res. 58:27–52, 1992.
Edelman, E. R., E. Mathiowitz, R. Langer, and M. Klagsbrun. Controlled and modulated release of basic fibroblast growth factor.Biomaterials 12:619–626, 1991.
Edgington, S. Angiogenic and angiostatic drugs: Reshaping biotech's future.Bio/tech. 10:981–985, 1992.
Flaumenhaft, R., and D. B. Rifkin. The extracellular regulation of growth factor action.Mol. Biol. Cell 3:1057–1065, 1992.
Forsten, K. E., and D. A. Lauffenburger. Autocrine ligand binding to cell receptors: Mathematical analysis of competition by solution decoys.Biophys. J. 61:518–529, 1992.
Forsten, K. E., and D. A. Lauffenburger. Interrupting autocrine ligand/receptor binding: Comparison between receptor blockers and ligand decoys.Biophys. J. 63:857–861, 1992.
Forsten, K. E., and D. A. Lauffenburger. Probability of autocrine ligand capture by cell surface receptors: implications for ligand secretion measurements.J. Comp. Biol. 1:15–23, 1994.
French, A. R., Sudlow, G., Wiley, H. S., and Lauffenburger, D. A. Postendocytic trafficking of EGF/EGF-receptor complexes is mediated through saturable and specific endosomal interactions.J. Biol. Chem. 269:15749–15755, 1994.
Harris, E. D.. Rheumatoid arthritis: pathophysiology and implications for therapy.N. Engl. J. Med. 322:1277–1289, 1990.
Hodgson, J.. Receptor screening and the search for new pharmaceuticals.Bio/tech. 10:973–980, 1993.
Hoffman, A. S. Molecular bioengineering of biomaterials in the 1990s and beyond: A growing liaison of polymers with molecular biology.Artif. Organs 16:43–49, 1992.
Ingber, D. E. The riddle of morphogenesis: A question of solution chemistry or molecular cell engineering?Cell 75: 1249–1252, 1993.
King, R. J., M. B. Jones, and M. Parviz. Regulation of lung cell proliferation by polypeptide growth factors.Am. J. Physiol. 257:L23-L38, 1989.
Knauer, D. J., H. S. Wiley, and D. D. Cunningham. Relationship between EGF-receptor occupancy and mitogenic response: Quantitative analysis using a steady-state model system.J. Biol. Chem. 259:5623–5631, 1984.
Kubuju, D. A., and L. G. Fine. Physiology and cell biology update: Polypeptide growth factors and their relation to renal disease.Am. J. Kidney Dis. 14:61–73, 1989.
Kuntz, I. D. Structure-based strategies for drug design and discovery.Science 257:1078–1082, 1992.
Langer, R., and J. P. Vacanti. Tissue engineering.Science 260:920–926, 1993.
Lauffenburger, D. A., and C. Cozens. Regulation of mammalian cell growth by autocrine growth factors: Analysis of consequences for inoculum cell density effects.Biotech. Bioeng. 33:1365–1378, 1989.
Lauffenburger, D. A., and J. J. Linderman. Receptors: Models for Binding, Trafficking and Signaling. New York: Oxford University Press, 1993.
Luyten, W. H. M. L., and J. E. Leysen. Receptor cloning and heterologous expression—Towards a new tool for drug discovery.Trends Biotech. 11:247–254, 1993.
Massia, S., and J. Hubbell. Covalent surface immobilization of arg-gly-asp- and tyr-ile-gly-ser-arg-containing peptides to obtain well-defined cell-adhesive substrates.Anal. Biochem. 187:292–301, 1990.
McGeady, M. L., S. Kerby, V. Shankar, F. Ciardiello, D. Salomon, and M. Seidman. Infection with a TGFα retroviral vector transforms ordinary mouse mammary epithelial cells but not normal rat fibroblasts.Oncogene 4:1375–1382, 1989.
Mendelsohn, J. Anti-epidermal growth factor receptor monoclonal antibodies as potential anti-cancer agents.J. Steroid Biochem. Mol. Biol. 37:889–892, 1990.
Meyer-Ingold, W. Wound therapy: Growth factors as agents to promote healing.Trends Biotech. 11:387–392, 1993.
Modjtahedi, H., J. Styles, and C. Dean. The growth response of human tumour cell lines expressing the EGF receptor to treatment with EGF and/or Mabs that block ligand binding.Int. J. Oncol. 3:237–243, 1993.
Morgan, R. A., and W. F. Anderson. Human gene therapy.Annu. Rev. Biochem. 62:191–217, 1993.
Moses, M., and R. Langer. Inhibitors of angiogenesis.Bio/Tech. 9:630–634, 1991.
Northrup, S. H., S. A. Allison, and J. A. McCammon. Brownian dynamics simulation of diffusion-influenced bimolecular reactions.J. Chem. Phys. 80:1517–1524, 1984.
Powell, E., M. R. Sobarzo, and W. M. Saltzman. Controlled release of nerve growth factor from a polymeric implant.Brain Res. 515:309–311, 1990.
Ratner, B. D. New ideas in biomaterials science—A path to engineered biomaterials.J. Biomed. Mat. Res. 27:837–850, 1993.
Robb, R. J. Human T-cell growth factor: Purification, biochemical characterization, and interaction with a cellular receptor.Immunobiology 161:21–50, 1982.
Rodeck, U., N. Williams, U. Murthy, and M. Herlyn. Monoclonal antibody 425 inhibits growth stimulation of carcinoma cells by exogenous EGF and tumor-derived EGF/TGFα.J. Cell. Biochem. 44:69–79, 1990.
Ross, R. The pathogenesis of atherosclerosis: An update.New Engl. J. Med. 314:488–500, 1986.
Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s.Nature 362:801–809, 1993.
Sieff, C. A. Biology and clinical aspects of the hematopoietic growth factors.Annu. Rev. Med. 41:483–496, 1990.
Sporn, M. B., and A. B. Roberts. Peptide growth factors and inflammation, tissue repair, and cancer.J. Clin. Invest. 78:329–332, 1986.
Sporn, M. B., and A. B. Roberts. Peptide growth factors are multifunctional.Nature 332:217–219, 1988.
Sporn, M. B., and A. B. Roberts. Autocrine secretion—10 years later.Ann. Intern Med. 117:408–414, 1992.
Sporn, M. B., and G. J. Todaro. Autocrine secretion and malignant transformation of cells.New Engl. J. Med. 303: 878–880, 1980.
Springer, T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm.Cell 76: 301–314, 1994.
ten Dijke, P, and K. K. Iwata. Growth factors for wound healing.Bio/tech. 7:793–797, 1989.
Tranquillo, R., M. Durrani, and A. Moon. Tissue engineering science: Consequences of cell traction force.Cytotechnology 10:225–250, 1992.
Wiley, H. S. Receptors: Topology, dynamics, and regulation. In: Membrane Dynamics and Signaling, edited by E. Bittner. JAI Press, 1992, pp. 113–142.
Wiley, H. S., J. J. Herbst, B. J. Walsh, D. A. Lauffenburger, M. G. Rosenfeld, and G. N. Gill. Role of tyrosine kinase activity in endocytosis, compartmentation, and downregulation of the EGF-receptor.J. Biol. Chem. 266: 11083–11094, 1991.
Yamada, Y., and G. Serrero. Autocrine growth induced by the insulin-related factor in the insulin-dependent teratoma cell line 1246-3A.Proc. Natl. Acad. Sci. USA 85:5936–5940, 1988.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lauffenburger, D.A., Forsten, K.E., Will, B. et al. Molecular/cell engineering approach to autocrine ligand control of cell function. Ann Biomed Eng 23, 208–215 (1995). https://doi.org/10.1007/BF02584423
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02584423