Glycosaminoglycan Synthesis by Wilms' Tumor

Hopwood, John J.; Dorfman, Albert

doi:10.1203/00006450-197801000-00013

Cited by 35 publications

(14 citation statements)

References 17 publications

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“…per h. This rate of accumulation is approx. 10-fold the rate of synthesis reported to occur in a hybrid mammalian cell culture line (Tomida et al, 1974), but 80-fold less than that reported in Wilm tumour (Hopwood & Dorfman, 1978) and 50-fold less than that noted in rat fibrosarcoma (Hopwood et al, 1974). Since degradation of hyaluronate occurs rapidly post partum, however, some degradation may already be occurring before delivery and thus the actual rate of synthesis may be even greater.…”

Section: Discussionmentioning

confidence: 56%

Pregnancy-related changes in rat cervical glycosaminoglycans

Golichowski¹,

King²,

Mascaro³

1980

Biochemical Journal

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Non-pregnant and pregnant rats of known gestational age were killed at intervals and their uterine cervices were excised and digested with papain. Glycosaminoglycans thus extracted were separated by cellulose acetate electrophoresis and stained with Alcian Blue. Glycosaminoglycans were identified by comparison with standards and by serial degradation with chondroitin ABC lyase, butyl nitrite and leech hyaluronidase. Dermatan sulphate, hyaluronic acid and heparan sulphate were identified and quantitatively determined by densitometry. The overall concentration of glycosaminoglycans changed little during pregnancy. A 3-fold total increase in uronic acid paralleled the increase in cervical weight. Hyaluronate content, however, increased 17-fold, and rose from 6% of total glycosaminoglycans in the non-pregnant state to 33% at term. Furthermore, the ratio of hyaluronate to hydroxyproline increased 10-fold. These changes are consistent with an accumulation of hyaluronate in the interstices between collagen fibres, resulting in the softening of this tissue that is seen in late pregnancy.

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Section: Discussionmentioning

confidence: 56%

Pregnancy-related changes in rat cervical glycosaminoglycans

Golichowski¹,

King²,

Mascaro³

1980

Biochemical Journal

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“…The stimulation of hyaluronate synthesis due to coculture is additive to that caused by serum (Table 1). These results provide an explanation for the observation that, although many types of tumors contain high concentrations of hyaluronate (2)(3)(4)(5)(6)(7)14), tumor or transformed cells in culture often produce only small amounts of this polysaccharide (11)(12)(13)(14). In these cases, it would seem likely that interactions between tumor cells and fibroblasts of the host are responsible for the high hyaluronate concentrations in the tumors.…”

Section: Stimulation Of Hyaluronate Synthesis In Cocultures Ofmentioning

confidence: 78%

“…Many tumors also contain elevated concentrations of chondroitin sulfates (2)(3)(4)(5)(6)(29)(30)(31)(32), presumably present as complex proteoglycans (31). Recent work by Iozzo (21) has shown that conditioned medium from cultures of colon carcinoma cells stimulates fibroblasts to produce increased In other studies (22), one of us has shown that interactions between fibroblasts and tumor cells also give rise to high levels of collagenase production.…”

Section: Discussionmentioning

confidence: 99%

Interactions between human tumor cells and fibroblasts stimulate hyaluronate synthesis.

Knudson¹,

Biswas²,

Toole³

1984

Proc. Natl. Acad. Sci. U.S.A.

183

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Several types of tumors contain high concentrations of hyaluronate, yet isolated tumor cells in culture often produce little glycosaminoglycan. To explore the possibility that interactions between tumor cells and host fibroblasts stimulate hyaluronate synthesis, human tumor cells were grown separately from and in coculture with normal human fibroblasts. Stimulation was observed with each of the three types of tumor cells used: LX-1 lung carcinoma, DAN pancreatic carcinoma, and TRIG melanoma. The interaction between LX-1 cells and fibroblasts was studied in detail. Under serum-free conditions, cocultures of LX-1 and fibroblasts synthesized 3-fold more hyaluronate than the sum of that produced by LX-1 and fibroblast cultures grown separately. This stimulation was linear over 72 hr and hyaluronate represented 80% of the glycosaminoglycan synthesized. Maximum stimulation occurred at a ratio of fibroblasts to LX-1 cells of 1-2:1. Quantitation of unlabeled glycosaminoglycans by HPLC analysis of disaccharides generated by digestion with chondroitin ABC and AC lyases (EC 4.2.2.4 and 4.2.2.5) demonstrated that net accumulation of hyaluronate increased 2-fold and that hyaluronate represented 80% of total chondroitinase-sensitive glycosaminoglycan produced by the cocultures. The disaccharide patterns obtaii*d showed that accumulations of chondroitin-4-and chondroitin-6-sulfates were stimulated proportionately to that of hyaluronate in these cocultures. Similar levels of stimulation due to coculture were obtained in serum-containing and serum-free media. Stimulation was not effected by addition of LX-1-conditioned medium to fibroblast cultures or by culturing LX.1 and fibroblasts under conditions where they shared the same medium but were physically separated. Cell contact between LX-1 and fibroblasts thus appears to be necessary for the stimulation of hyaluronate synthesis.Hyaluronate is present in high concentrations in the extracellular matrix surrounding migrating and proliferating cells during development of embryonic tissues and organs and during regeneration or healing in adult tissues (1). Hyaluronate is also present in large amounts in several types of tumors-e.g., Wilm (2), mammary (3), hepatic (4), lung (5), and parotid gland (6) tumors in humans. In a previous study (7), we showed that a high concentration of hyaluronate accumulates in the V2-carcinoma grown in the rabbit, under conditions where it is highly invasive. In comparison, much lower amounts of hyaluronate were found when the same tumor was grown in the nude mouse, where it is noninvasive. These findings suggest that hyaluronate may be associated with the invasive behavior of malignant tumors. Thus we have begun to investigate the regulation of hyaluronate metabolism during tumorigenesis.Hyaluronate is actively synthesized by some transformed and tumor cell lines in culture (8-10) but this property is not common to all tumorigenic cells. We have found that simian virus-transformed 3T3 cells and polyoma-transformed BHK cells produce far less hya...

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“…Others have described the presence of high concentrations of hyaluronate and other GAG in tumors (40)(41)(42)(43) and their production by transformed or tumor cells in vitro (23,(44)(45)(46)(47)(48) (1-11, 15, 37 …”

Section: Resultsmentioning

confidence: 99%

Hyaluronate and invasiveness of the rabbit V2 carcinoma.

Toole¹,

Biswas²,

Gross³

1979

Proc. Natl. Acad. Sci. U.S.A.

208

110

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We propose that hyaluronate, a major component of extracellular matrices through which cells migrate during embryonic tissue development and in regenerative processes, is also concentrated in the environment through which neoplastic cells invade local host tissues and may facilitate this process. The hyaluronate content of invasive V2 carcinoma grown in rabbit was found to be 34 times greater than that of the same tumor grown in the nude mouse, in which it is noninvasive. Moreover, hyaluronate concentrations were most elevated in the connective tissue interface between the tumor mass and the neighboring host tissue in the invasive rabbit tumors. The particular site of tumor implantation in the rabbit or nude mouse did not affect the concentrations of hyaluronate in either the parenchyma or the surrounding connective tissue. Similar values were obtained for neoplasms grown in muscle, which normally contains little hyaluronate, and in subcutaneous tissue, which is relatively rich in this glycosaminoglycan. The extracellular environment through which cells migrate during embryonic development and repair processes is enriched in the glycosaminoglycan (GAG) hyaluronate. Examples are found in the developing embryonic cornea (1), sclerotome (2), neural crest (3-5), heart (6, 7), and primary mesenchyme (8), as well as in regenerating salamander limb (9), regenerating rabbit tendon (10), and bone fracture callus (11). In certain of these tissues-e.g., the embryonic cornea (1) and neural crest (3-5, 12)-a close correlation between high concentrations of hyaluronate, high levels of hydration, and increased matrix volume with cell migration has been observed. On the basis of these studies we have proposed (i) that, due to its unique hydrodynamic properties (13), hyaluronate exerts a swelling pressure that can cause alterations in the size of intercellular spaces and separation of cell and connective tissue layers, thus opening avenues for cell migration, and (ii) that hyaluronate binds to the surface of cells (14), influencing specific cell interactions that might regulate the timing of cell assembly and differentiation (for review, see ref. 15).We are now examining the proposition that tumor cell migration into neighboring host tissue (i.e., invasion) also requires a hyaluronate-enriched environment. Previous studies in this laboratory of the cellular source of collagenase in the V2 carcinoma compared this neoplasm in the rabbit with that in the nude mouse (C. Biswas, K. J. Bloch, and J. Gross, unpublished results). Histological examination showed infiltration of tumor cells into and beyond the surrounding connective tissue (here called "capsule") of the rabbit tumors but not that of the nude mouse tumors. The capsules of the latter appeared to be intact around the entire neoplasm whereas, in the rabbit, sections of the tumor-host interface were fused, giving rise to discontinuities in the capsule and infiltration of tumor cells. The rabbit intramuscular and subcutaneous tumors have also been shown to be reproduc...

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Glycosaminoglycan Synthesis by Wilms' Tumor

Abstract: Summaryand collagenase (sterile, Clostridium histolvticum) were obtained

Cited by 35 publications

References 17 publications

Pregnancy-related changes in rat cervical glycosaminoglycans

Pregnancy-related changes in rat cervical glycosaminoglycans

Interactions between human tumor cells and fibroblasts stimulate hyaluronate synthesis.

Hyaluronate and invasiveness of the rabbit V2 carcinoma.

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