A theoretical framework is proposed for the analysis of adhesion between cells or of cells to surfaces when the adhesion is mediated by reversible bonds between specific molecules such as antigen and antibody, lectin and carbohydrate, or enzyme and substrate. From a knowledge of the reaction rates for reactants in solution and of their diffusion constants both in solution and on membranes, it is possible to estimate reaction rates for membrane-bound reactants. Two models are developed for predicting the rate of bond formation between cells and are compared with experiments. The force required to separate two cells is shown to be greater than the expected electrical forces between cells, and of the same order of magnitude as the forces required to pull gangliosides and perhaps some integral membrane proteins out of the cell membrane.

https://science.sciencemag.org/content/sci/200/4342/618.full.pdf

Models for the specific adhesion of cells to cells

The development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation. Blood vessel neoformation is also important in the pathogenesis of many disorders, particularly rapid growth and metastasis of solid tumours. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-alpha and transforming factors-alpha and -beta. But it is unclear whether any of these agents actually mediates angiogenesis and tumour growth in vivo. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenesis inducer released by a variety of tumour cells and expressed in human tumours in situ. To test whether VEGF may be a tumour angiogenesis factor in vivo, we injected human rhabdomyosarcoma, glioblastoma multiforme or leiomyosarcoma cell lines into nude mice. We report here that treatment with a monoclonal antibody specific for VEGF inhibited the growth of the tumours, but had no effect on the growth rate of the tumour cells in vitro. The density of vessels was decreased in the antibody-treated tumours. These findings demonstrate that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.

Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo

Genistein, a specific inhibitor of tyrosine-specific protein kinases.

/pdf/inositol-trisphosphate-and-diacylglycerol-as-second-4drzjsg27y.pdf

Inositol trisphosphate and diacylglycerol as second messengers.

Epidermal growth factor-related peptides and their receptors in human malignancies

The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.

https://cancerres.aacrjournals.org/content/canres/44/2/753.full.pdf

Expression of Epidermal Growth Factor Receptors in Human Brain Tumors

Dynamics of fluorescence marker concentration as a probe of mobility

We have made direct, quantitative measurements of the lateral motion and age-dependent distribution of acetylcholine receptors (AChR) on the surface of rat myotubes in primary culture. AChR were fluorescently marked with tetramethylrhodamine-labeled alpha-bungarotoxin and AChR lateral motion was measured by the fluoresence photobleaching recovery technique. We found two coexisting distinct classes of AChR: (i) mobile, uniformly distributed AChR that appear on all myotubes shortly after fusion from myoblasts; and (ii) immobile, dense, highly granular AChR in patches of 10-60 mum size that appear shortly after fusion and disappear after myotubes have become extensively interconnected. In addition, evidence of turnover of AChR labeled with tetramethylrhodamine-alpha-bungarotoxin is seen in the gradual internalization of surface fluorescence within 36 hr after labeling. The relevance of these results to an understanding of the membrane dynamics and localization of muscle AChR is discussed.

https://www.pnas.org/content/pnas/73/12/4594.full.pdf

Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers.

Formal proof for an involvement of autocrine stimulation in the disturbed growth of malignant cells has been difficult to obtain, in part due to lack of precise methods of assessing growth factor production and receptor occurrence. In this study we have analyzed the mRNA levels for two growth factors and the corresponding receptors in a number of established human malignant glioma cell lines. Twenty-one tested lines all contained transcripts for the platelet-derived growth factor (PDGF) A chain while 16-17 of 21 expressed the c-sis/PDGF B chain gene; these two genes were expressed independently of each other. PDGF receptor transcripts were present in 15-16 of the 21 lines. Transcripts for the epidermal growth factor receptor were found in all 15 tested lines, in 2 of them at high levels, and the corresponding ligand transforming growth factor-alpha was found in 11 of 15 lines. No amplification or structural rearrangements of the genes, as analyzed by Southern blot hybridization, could explain the varying expression of PDGF A and B chain transcripts or the elevated levels of epidermal growth factor receptor mRNA. A correlation was found between cell morphology and expression of growth factor and receptor mRNA in these lines. The highest amount of PDGF receptor transcripts was found in cells with fibroblast-like morphology, and c-sis/B chain transcripts were found in small cell types and in cells with astrocyte-like morphology, while no clear relationship was found between PDGF receptor and A chain transcript levels or between morphology and A chain transcripts. It is possible that the findings reflect a coordinated expression of these genes in the progenitor cells. In conclusion, the data imply the existence of two possible autocrine loops in human malignant glioma lines, affecting the PDGF and epidermal growth factor receptor pathways.

https://cancerres.aacrjournals.org/content/canres/48/14/3910.full.pdf

Expression of Messenger RNAs for Platelet-derived Growth Factor and Transforming Growth Factor-α and Their Receptors in Human Malignant Glioma Cell Lines

J Schlessinger

Papers

Expression of Epidermal Growth Factor Receptors in Human Brain Tumors

Dynamics of fluorescence marker concentration as a probe of mobility

Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers.

Expression of Messenger RNAs for Platelet-derived Growth Factor and Transforming Growth Factor-α and Their Receptors in Human Malignant Glioma Cell Lines

Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies.