High Concentration Of Hyaluronic Acid Research Articles

Contribution of the extracellular matrix to growth properties of cells from a preneoplastic outgrowth: possible role of hyaluronic acid.

Hyaluronic acid (HA) accumulates around actively growing normal and tumorigenic mammary epithelial cells and has been implicated as a modulator of cell proliferation. We have tested the role of exogenous HA presented in several different forms in in vitro growth regulation of a cell line (CL-S1) derived from preneoplastic mouse mammary tissue. This cell line grows slowly and synthesizes very little HA. We first assessed growth of CL-S1 cells seeded onto actual matrix generated by CL-S1 cells themselves (which has a low HA content) or by a related tumorigenic cell line, +SA, that generates an HA-rich matrix. Growth on both these HA-containing substrata was significantly enhanced above control values on plastic. Growth on the +SA biomatrix was over 5 times greater than on tissue culture plastic and significantly greater than that seen with all other treatments. Differences in growth responses of CL-S1 cells seeded atop CL-S1- and +SA-derived matrices could be attributable to differences in matrix HA content. As a more direct test of this possibility, growth responses of CL-S1 cells to HA covalently bonded to tissue culture dishes and to HA dissolved in culture media were tested. Growth on the prepared HA substrata was consistently twice that on plastic. In soluble form, HA at a concentration of 100 micrograms HA/ml culture medium, stimulated CL-S1 growth 196 and 125% of control in monolayer cultures, respectively, seeded at low (approximately equal to 10(2) viable cells/cm2) and high (approximately equal to 10(4) viable cells/cm2) densities on plastic. Higher HA concentrations inhibited growth at low seeding densities.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperviscosity caused by hyaluronic acid in serum in a case of Wilms' tumor.

We describe the case of a three-year-old girl with Wilms' tumor, whose serum showed at least a fivefold increase in relative viscosity although concentrations of albumin and immunoglobulins were normal. An unusual electrophoretogram of serum protein prompted further investigation. The increased viscosity was caused by the presence of high concentrations of hyaluronic acid, a glycosaminoglycan normally not detectable in serum.

A role for glycosaminoglycans in the development of collagen fibrils

Extensive data on the glycosaminoglycan (GAG) composition and the collagen fibril diameter distribution have been collected for a diverse range of connective tissues. It is shown that tissues with the smallest diameter collagen fibrils (mass-average diameter < 60 nm) have high concentrations of hyaluronic acid and that tissues with the largest diameter collagen fibrils (mass-average diameter ∼200 nm) have high concentrations of dermatan sulphate. It is suggested that the lateral growth of fibrils beyond a diameter of about 60 nm is inhibited by the presence of an excess of hyaluronic acid but that this inhibitory effect may be removed by an increasing concentration of chondroitin sulphate and/or dermatan sulphate. It is also postulated that high concentrations of chondroitin sulphate will inhibit fibril growth beyond a mass-average diameter of ∼150 nm. Such an inhibition may in turn be removed by an increasing concentration of dermatan sulphate such that it becomes the dominant GAG present in the tissue.

Electrophoresis of tissue glycosaminoglycans as an aid in the diagnosis of mesotheliomas

The histologic distinction between mesotheliomas and adenocarcinomas on mesothelial surfaces is sometimes difficult. High concentrations of hyaluronic acid in pleural and peritoneal fluids of mesothelioma patients have been reported. This paper describes results of glycosaminoglycan electrophoresis of papain digests of 7 mesotheliomas and 27 other tumors. Either all or almost all demonstrable glycosaminoglycans in mesotherliomas was hyaluronic acid. Control tissues had variable electrophoretic patterns showing other glycosaminoglycans in addition to hyaluronic acid. In the clinical context of differentiating mesotheliomas and adenocarcinomas in tissue samples, this technique seems simple, economical, and relatively specific.

Histochemistry of glycosaminoglycans in the skin and oral mucosa of the rat

The distribution of glycosaminoglycans (GAGs) was studied by staining with the alcian blue-critical electrolyte concentration, alcian blue-pH, aldehyde fuchsin and modified periodic acid-Schiff procedures. GAGs were identified by specific removal from sections with testicular hyaluronidase, chondroitinase ABC or nitrous acid. Dermatan sulphate was associated with collagen in skin and all regions of the oral mucosa. A high concentration of hyaluronic acid was present in the antemolar rugae of the palate and the connective tissue papillae of the posterior rugae of the palate contained a high density of sulphated GAG between plump cells but not associated with collagen. This GAG, possibly chondroitin sulphate, seemed similar to that in the papillae of hair bulbs.

Seasonal variations in the susceptibility of the aortic wall to atherosclerosis Biochemical studies of glycosaminoglycans and collagen of rabbit atherosclerosis

The aortic content of glycosaminoglycans and collagen as well as the uptake of [ 125I] albumin were studied in 53 male albino rabbits during hair-shedding and outside the period of hair-shedding to elucidate the previously reported resistance to experimental arteriosclerosis during the shedding period [1]. The concentration of hyaluronic acid was highest during hair-shedding, decreasing towards the non-shedding period. The content of dermatan sulphate, chondroitin, 6-sulphate and hydroxyproline was lowest during shedding and highest outside the shedding period. Accordingly, the incorporation of [ 35S] sulphate in chondroitin-4,6-sulphate and the dermatan plus heparan sulphate fraction was increased outside shedding, consistent with a stimulated synthesis. The concentration of hyaluronic acid was negatively correlated to the uptake of [ 125I] albumin, and the dermatan sulphate content was positively correlated to the content of hydroxyproline. The higher concentration of hyaluronic acid during the period of shedding may improve the elastic properties as well as the ability of the aortic wall to absorbe the haemodynamic strain involved in the vascular injury of this type of experimental arteriosclerosis [2]. The decrease in the concentration of hyaluronic acid simultaneously with an increase in the aortic content of collagen as well as of chondroitin-4, 6-sulphate and dermatan sulphate may imply a greater stiffness of the aorta resulting in a higher susceptibility to injury. The relationship between hyaluronic acid and [ 125I] albumin is consistent with an importance of hyaluronic acid to the susceptibility of the arterial wall to deposition of macromolecules such as the lipids. Our observations represent an example of endogenous conditioned variations in the aortic content of glycosaminoglycans and hydroxyproline accompanied by a variation in the susceptibility to experimental arteriosclerosis.

Mucopolysaccharides in relation to growth and thyroid hormones

It may be stated that homeostasis of acid mucopolysaccharides occurs if the requirements of the connective tissues for the hormones are supplied. The participation of insulin in the maintenance of normal levels and normal turnover of acid mucopolysaccharides in skin has been described in a previous publication [28]. The requirement for thyroxine was documented in the present communication by demonstrating that its administration restored the defects in mucopolysaccharide metabolism observed in the hypothyroid animal. The decreased turnover of chondroitinsulfuric acid in hypophysectomized rats was effectively reversed by injection of growth hormone. However, the abnormally high concentration of hyaluronic acid was increased further by this treatment. Evidently, administration of growth hormone alone did not create a favorable endocrine environment in the hypophysectomized animal for the restoration of hyaluronic acid metabolism to normal. Although no direct experimental evidence has been presented, it is suggested that maintenance of normal concentrations of hyaluronic acid depends upon an adequate supply of both growth hormone and thyroxine. Taurog et al. [42] have demonstrated that secretion of thyroid hormones is reduced by more than 90 per cent in the hypophysectomized rat. Since hypothyroidism is a conspicuous manifestation of pituitary deficiency, it was not unexpected to find that the alterations in mucopolysaccharide metabolism were similar in both conditions. These studies demonstrate undeniably an influence of hormones on acid mucopolysaccharide metabolism. However, they reveal no unanimity of hormone-enzyme relationships on the biosynthetic or degradative processes involved. In the diabetic rat and in the animal receiving cortisone, the metabolism of both mucopolysaccharides is depressed suggesting a common fundamental defect in the early stages of synthesis. On the other hand, the differential effects of growth hormone and thyroxine on hyaluronic acid and chondroitinsulfuric acid metabolism leads one to conclude that these hormones exert their effects on later stages of synthesis or on degradative pathways.