heparitin-sulfate and Carcinoma

Cell surface proteoglycans are known to be important regulators of many aspects of cell behavior. The principal family of transmembrane proteoglycans is the syndecans, of which there are four in mammals. Syndecan-1 is mostly restricted to epithelia, and bears heparan sulfate chains that are capable of interacting with a large array of polypeptides, including extracellular matrix components and potent mediators of proliferation, adhesion and migration. For this reason, it has been studied extensively with respect to carcinomas and tumor progression. Frequently, but not always, syndecan-1 levels decrease as tumor grade, stage and invasiveness and dedifferentiation increase. This parallels experiments that show depletion of syndecan-1 can be accompanied by loss of cadherin-mediated adhesion. However, in some tumors, levels of syndecan-1 increase, but the characterization of its distribution is relevant. There can be loss of membrane staining, but acquisition of cytoplasmic and/or nuclear staining that is abnormal. Moreover, the appearance of syndecan-1 in the tumor stroma, either associated with its cellular component or the collagenous matrix, is nearly always a sign of poor prognosis. Given its relevance to myeloma progression, syndecan-1-directed antibody-toxin conjugates are being tested in clinical and preclinical trials, and may have future relevance to some carcinomas.

Topics: Animals; Carcinoma; Epithelial-Mesenchymal Transition; Glycosaminoglycans; Heparitin Sulfate; Humans; Proteoglycans; Syndecan-1

Fibrolamellar carcinomas (FLCs), lethal tumors occurring in children to young adults, have genetic signatures implicating derivation from biliary tree stem cell (BTSC) subpopulations, co-hepato/pancreatic stem cells, involved in hepatic and pancreatic regeneration. FLCs and BTSCs express pluripotency genes, endodermal transcription factors, and stem cell surface, cytoplasmic and proliferation biomarkers. The FLC-PDX model, FLC-TD-2010, is driven ex vivo to express pancreatic acinar traits, hypothesized responsible for this model's propensity for enzymatic degradation of cultures. A stable ex vivo model of FLC-TD-2010 was achieved using organoids in serum-free Kubota's Medium (KM) supplemented with 0.1% hyaluronans (KM/HA). Heparins (10 ng/ml) caused slow expansion of organoids with doubling times of ∼7-9 days. Spheroids, organoids depleted of mesenchymal cells, survived indefinitely in KM/HA in a state of growth arrest for more than 2 months. Expansion was restored with FLCs co-cultured with mesenchymal cell precursors in a ratio of 3:7, implicating paracrine signaling. Signals identified included FGFs, VEGFs, EGFs, Wnts, and others, produced by associated stellate and endothelial cell precursors. Fifty-three, unique heparan sulfate (HS) oligosaccharides were synthesized, assessed for formation of high affinity complexes with paracrine signals, and each complex screened for biological activity(ies) on organoids. Ten distinct HS-oligosaccharides, all 10-12 mers or larger, and in specific paracrine signal complexes elicited particular biological responses. Of note, complexes of paracrine signals and 3-O sulfated HS-oligosaccharides elicited slowed growth, and with Wnt3a, elicited growth arrest of organoids for months. If future efforts are used to prepare HS-oligosaccharides resistant to breakdown in vivo, then [paracrine signal-HS-oligosaccharide] complexes are potential therapeutic agents for clinical treatments of FLCs, an exciting prospect for a deadly disease.

Topics: Carcinoma; Child; Heparitin Sulfate; Humans; Oligosaccharides; Paracrine Communication; Sulfates

HS (heparan sulfate) is a long linear polysaccharide, variably modified by epimerization and sulfation reactions, and is organized into different domains defined by the extent of modification. To further elucidate HS structural organization, the relative position of different HS structures, identified by a set of phage-display-derived anti-HS antibodies, was established. Two strategies were employed: inhibition of HS biosynthesis using 4-deoxy-GlcNAc, followed by resynthesis, and limited degradation of HS using heparinases. Using both approaches, information about the position of antibody-defined HS structures was identified. The HS structure recognized by the antibody NS4F5, rigorously identified as (GlcN6S-IdoA2S)₃, was found towards the non-reducing end of the HS chain.

Topics: Animals; Bacterial Proteins; Carcinoma; Cell Line, Tumor; Deoxyglucose; Enzyme Inhibitors; Epitope Mapping; Flavobacterium; Glucosamine; Heparin Lyase; Heparitin Sulfate; Humans; Hydrolysis; Immunohistochemistry; Kidney; Kinetics; Male; Melanoma; Molecular Structure; Rats; Rats, Wistar

Several angiogenic growth factors including fibroblast growth factors 1 and 2 (FGF1 and FGF2) depend on heparan sulphate (HS) for biological activity. We previously showed that all cellular elements in ovarian tumour tissue synthesised HS but biologically active HS (i.e. HS capable of binding FGF2 and its receptor) was confined to ovarian tumour endothelium. In this study, we have sought to explain this observation. Heparan sulphate sulphotransferases 1 and 2 (HS6ST1 and HS6ST2) attach sulphate groups to C-6 of glucosamine residues in HS that are critical for FGF2 activation. These enzymes were strongly expressed by tumour cells, but only HS6ST1 was found in endothelial cells. Immunostaining with the 3G10 antibody of tissue sections pretreated with heparinases indicated that HS proteoglycans were produced by tumour and endothelial cells. These results indicated that, in contrast to the endothelium, HS produced by tumour cells may be modified by cell-surface heparanase (HPA1) or endosulphatase (SULF). Protein and RNA analysis revealed that HPA1 was strongly expressed by ovarian tumour cells in eight of ten specimens examined. HSULF-1, which removes specific 6-O-sulphate groups from HS, was abundant in tumour cells but weakly expressed in the endothelium. If this enzyme was responsible for the lack of biologically active HS on the tumour cell surface, we would expect exogenous FGF2 binding to be preserved; we showed previously that this was indeed the case although FGF2 binding was reduced compared to the endothelium and stroma. Thus, the combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes.

Topics: Carcinoma; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glucuronidase; Heparitin Sulfate; Humans; In Situ Hybridization; Ovarian Neoplasms; RNA, Messenger; Sulfotransferases

The S-nitrosylated proteoglycan glypican-1 recycles via endosomes where its heparan sulfate chains are degraded into anhydromannose-containing saccharides by NO-catalyzed deaminative cleavage. Because heparan sulfate chains can be associated with intracellular protein aggregates, glypican-1 autoprocessing may be involved in the clearance of misfolded recycling proteins. Here we have arrested and then reactivated NO-catalyzed cleavage in the absence or presence of proteasome inhibitors and analyzed the products present in endosomes or co-precipitating with proteasomes using metabolic radiolabeling and immunomagnet isolation as well as by confocal immunofluorescence microscopy. Upon reactivation of deaminative cleavage in T24 carcinoma cells, [(35)S]sulfate-labeled degradation products appeared in Rab7-positive vesicles and co-precipitated with a 20 S proteasome subunit. Simultaneous inhibition of proteasome activity resulted in a sustained accumulation of degradation products. We also demonstrated that the anhydromannose-containing heparan sulfate degradation products are detected by a hydrazide-based method that also identifies oxidized, i.e. carbonylated, proteins that are normally degraded in proteasomes. Upon inhibition of proteasome activity, pronounced colocalization between carbonyl-staining, anhydro-mannose-containing degradation products, and proteasomes was observed in both T24 carcinoma and N2a neuroblastoma cells. The deaminatively generated products that co-precipitated with the proteasomal subunit contained heparan sulfate but were larger than heparan sulfate oligosaccharides and resistant to both acid and alkali. However, proteolytic degradation released heparan sulfate oligosaccharides. In Niemann-Pick C-1 fibroblasts, where deaminative degradation of heparan sulfate is defective, carbonylated proteins were abundant. Moreover, when glypican-1 expression was silenced in normal fibroblasts, the level of carbonylated proteins increased raising the possibility that deaminative heparan sulfate degradation is involved in the clearance of misfolded proteins.

Topics: Animals; Carcinoma; Cell Line; Cell Line, Tumor; Cell Membrane; Endosomes; Fibroblasts; Glypicans; Heparitin Sulfate; Humans; Mice; Microscopy, Confocal; Models, Biological; Neuroblastoma; Oxidation-Reduction; Proteasome Endopeptidase Complex; Protein Binding; Proteins; Sulfates

The chondroitin sulfate excreted in the urine of 10 patients with cancer of the head and neck and 27 healthy subjects was analyzed. The disaccharide products formed from chondroitin sulfate excreted by these 10 patients by action of chondroitinase ABC show a significant (P < 0.0001) relative increase of nonsulfated disaccharide (35.6% +/- 5.7%) when compared with the nonsulfated disaccharide (10.0% +/- 0.9%) present in the chondroitin sulfate of 27 healthy subjects. In 6 patients the structure of the excreted compound was analyzed up to 4 months after surgery. After removal of the cancer, the percent amounts of the nonsulfated disaccharide tend to approach the values found for the chondroitin sulfate of healthy subjects. A significant (P < 0.0001) change in the ratio of urinary chondroitin sulfate and heparan sulfate and a decrease in the electrophoretic migration of chondroitin sulfate were also observed. All of the patients with head and neck cancer analyzed so far have shown this structural anomaly of urinary chondroitin sulfate. This assay may be useful in the diagnosis and follow-up of cancer therapy.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Chondroitin Sulfates; Chromatography; Electrophoresis; Head and Neck Neoplasms; Heparitin Sulfate; Humans; Middle Aged

Basic fibroblast growth factor (bFGF) is dependent on heparan sulphate for its ability to activate the cell surface signal transducing receptor. We have investigated the FGF dual receptor mechanism in a novel model of the transformation from human colon adenoma to carcinoma in vitro. Reverse transcription-polymerase chain reaction showed that mRNA for FGF receptors 1 and 2 were expressed in both the adenoma and carcinoma cells whereas immunocytochemistry showed that the expression of the FGF R1 was reduced significantly in the carcinoma cells. We have reported previously that the composition and sequence of human colon adenoma and carcinoma heparan sulphate (HS) differ in a defined and specific manner. The functional significance of these changes was assessed by affinity co-electrophoresis, which showed that the affinity of adenoma HS for bFGF was 10-fold greater than that of the carcinoma HS (Kd 220 nM vs. 2493 nM, respectively). In addition, Northern studies of the expression of syndecan 1 and 4 mRNA showed that proteoglycan core protein expression was reduced significantly in the carcinoma cells. These findings were associated with a reduced biological response to bFGF in the carcinoma cells that could be partially reversed by the addition of exogenous heparin, suggesting that both the proteoglycan and signal transducing receptor control the cells' response to bFGF.

Topics: Adenoma; Carcinoma; Colonic Neoplasms; Disease Progression; Down-Regulation; Fibroblast Growth Factor 2; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Heparin; Heparitin Sulfate; Humans; Neoplasm Proteins; Proteoglycans; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Signal Transduction; Tumor Cells, Cultured

Invasive growth of cancer cells is a complex process involving specific interactions between tumour cells and the orderly, integrated complexes of the extracellular matrix. Basement membranes have been proposed as one constituent of extracellular matrix which carries responsibility for regulating invasion and metastasis. Using a chemically induced rat tongue carcinoma model, it has been shown that components of the basement membrane and its overall structure are altered during tumour invasion, and methods have been developed to quantitate some of these differences. Since the basement membrane can be specifically characterized by its fibrous protein network of Type IV collagen and laminin, which is embedded in a heparan sulphate-rich proteoglycan matrix, these components have been targeted. In particular, the current paper presents results in the context of current concepts of early changes in neoplastic invasion of underlying connective tissues. In consequence, further elaboration of the underlying mechanisms of epithelial migration in oral cancer may allow an exploration of the use of alterations in expression of basement membrane components as prognostic indicators.

Topics: 4-Nitroquinoline-1-oxide; Animals; Basement Membrane; Carcinogens; Carcinoma; Cell Movement; Collagen; Coloring Agents; Connective Tissue; Disease Models, Animal; Epithelium; Extracellular Matrix; Extracellular Matrix Proteins; Heparitin Sulfate; Immunohistochemistry; Laminin; Neoplasm Invasiveness; Polylysine; Proteoglycans; Rats; Tongue Neoplasms

We report a detailed analysis of heparan sulfate (HS) structure using a model of human colon carcinogenesis. Metabolically radiolabeled HS was isolated from adenoma and carcinoma cells. The chain length of HS was the same in both cell populations (Mr 20,000; 45-50 disaccharides), and the chains contained on average of two sulfated domains (S domains), identified by heparinase I scission. This enzyme produced fragments of approximate size 7 kDa, suggesting that the S domains were evenly spaced in the intact HS chain. The degree of polymer sulfation and the patterns of sulfation were strikingly different between the two HS species. When compared with adenoma HS, the iduronic acid 2-O-sulfate content of the carcinoma-derived material was reduced by 33%, and the overall level of N-sulfation was reduced by 20%. However, the level of 6-O-sulfation was increased by 24%, and this was almost entirely attributable to an enhanced level of N-sulfated glucosamine 6-O-sulfate, a species whose data implied was mainly located in the mixed sequences of alternating N-sulfated and N-acetylated disaccharides. The results indicate that in the transition to malignancy in human colon adenoma cells, the overall molecular organization of HS is preserved, but there are distinct modifications in both the S domains and their flanking mixed domains that may contribute to the aberrant behavior of the cancer cell.

Topics: Adenoma; Carcinoma; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Colonic Neoplasms; Heparitin Sulfate; Humans; Molecular Structure; Molecular Weight; Nitrous Acid; Oligosaccharides; Tumor Cells, Cultured

Perlecan, a ubiquitous heparan sulfate proteoglycan, possesses angiogenic and growth-promoting attributes primarily by acting as a coreceptor for basic fibroblast growth factor (FGF-2). In this report we blocked perlecan expression by using either constitutive CMV-driven or doxycycline- inducible antisense constructs. Growth of colon carcinoma cells was markedly attenuated upon obliteration of perlecan gene expression and these effects correlated with reduced responsiveness to and affinity for mitogenic keratinocyte growth factor (FGF-7). Exogenous perlecan effectively reconstituted the activity of FGF-7 in the perlecan-deficient cells. Moreover, soluble FGF-7 specifically bound immobilized perlecan in a heparan sulfate-independent manner. In both tumor xenografts induced by human colon carcinoma cells and tumor allografts induced by highly invasive mouse melanoma cells, perlecan suppression caused substantial inhibition of tumor growth and neovascularization. Thus, perlecan is a potent inducer of tumor growth and angiogenesis in vivo and therapeutic interventions targeting this key modulator of tumor progression may improve cancer treatment.

Topics: Animals; Carcinoma; Colonic Neoplasms; DNA, Antisense; Fibroblast Growth Factor 10; Fibroblast Growth Factor 2; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Gene Expression; Growth Substances; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Melanoma, Experimental; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Neovascularization, Pathologic; Protein Binding; Proteoglycans

Undifferentiated HT29 and differentiated HT29G-human colon carcinoma cells have been used to study the changes in proteoglycan production and structure associated with enterocytic cell differentiation. Differentiated cells incorporate twice as much sulfate than undifferentiated cells when labeled with [35S]sulfate. Both cell lines produce a heparan sulfate proteoglycan which was purified by ion-exchange. The heparan sulfate proteoglycan from differentiated HT29G- cells is larger and more homogeneous in size than that produced by undifferentiated HT29 cells. No differences in the core protein structure were observed. The detailed structural analysis of the heparan sulfate chains revealed that the structure of these chains follows the standard rules for these glycosaminoglycans with N-sulfated domains and N-acetylated domains. The main finding was that differentiated HT29G- cells have a degree of higher sulfation than HT29 cells. These differences were found to affect primarily 6-O-sulfated positions.

Topics: Carcinoma; Cell Differentiation; Chromatography, Gel; Chromatography, Ion Exchange; Colonic Neoplasms; Heparan Sulfate Proteoglycans; Heparitin Sulfate; HT29 Cells; Humans; Proteoglycans; Sulfates

We investigated changes in the glycosaminoglycans (GAGs) during progression of a human gingival carcinoma xenograft line, GK -1, in nude mice. The GAGs extracted from cancers 3, 5, 7, 10 and 15 weeks after transplantation consisted of hyaluronic acid (HA), chondroitin sulfate (CS) and heparan sulfate (HS) as major components, and dermatan sulfate (DS) as a trace component for all cancers. HPLC analysis revealed that the HA content per defatted tissue dry weight increased in the cancers 5 weeks after transplantation compared to those of 3 weeks (p < 0.05), while CS for cancers at 10 weeks decreased compared with 7 weeks (p < 0.05). However, HS showed no significant change. Both the CS and DS contained primarily 4-sulfated disaccharide units. Immunohistochemical staining with antibody 2-B-6 for the PGs having delta DI-4S produced by chondroitinase ABC digestion showed that CS is located in the tissue surrounding the cancer nests and mass. These results indicate that the location of accumulation of CS, which primarily contains 4-sulfated disaccharide units, plays an important role in cancer progression.

Topics: Animals; Carcinoma; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Disaccharides; Disease Progression; Female; Gingival Neoplasms; Glycosaminoglycans; Heparitin Sulfate; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplasm Transplantation; Tumor Cells, Cultured

A Lewis lung carcinoma-derived low metastatic clone, P29, with a capacity to induce a fibrotic stromal response of host tissue, exhibits tumorigenesis depending on an interstitial matrix formed by the induced stromal cells. Using this clone, in the present study we isolated and characterized a membrane-intercalated proteoglycan that mediates interaction between the tumor cells and interstitial matrix. The tumor cells were cultured in the presence of [3H]glucosamine and [35S]sulfate or [35S]methionine, and hydrophobic proteoglycans were isolated by chromatography on DEAE-Sephacel and then Octyl-Sepharose CL-4B. Proteoglycans with high affinity to the octylresidue were obtained from the cell layer but not to any significant extent from the medium. By CsCl density gradient centrifugation, they were separated into bottom, middle, and top subfractions, which were shown to consist of homogeneous species with estimated M(r) values of 270,000 (named CPGIIIB), 200,000 (CPGIIIM), and 195,000 (CPGIIIT), respectively, by gel filtration on Sepharose CL-4B. These proteoglycans were intercalated into phosphatidylcholine liposomes, suggesting that they are all membrane-intercalated proteoglycans. Analyses of their glycosaminoglycans with chondroitinase ABC and heparitinase I plus II demonstrated that they all contain heparan sulfate as a major glycosaminoglycan (58-85%) and chondroitin 4-sulfate as a minor one (15-42%). Of these three proteoglycans, only CPGIIIB proteoglycan bound specifically to fibronectin-Sepharose 4B under physiological conditions. Molecular analyses of this proteoglycan by Sepharose CL-4B or SDS-PAGE before and after treatments with glycosaminoglycan degradation enzymes or trifluoromethanesulfonic acid demonstrated that CPGIIIB proteoglycan is a hybrid proteoglycan having heparan sulfate and chondroitin 4-sulfate chains on the same core protein with an M(r) of 40,000. Affinity chromatographies of the CPGIIIB proteoglycan on fibronectin-Sepharose 4B after treatments with these enzymes demonstrated that it bound to fibronectin via its heparan sulfate chains. On the basis of the above results, we propose that the CPGIIIB proteoglycan mediates the interaction between the tumor cells and interstitial matrix.

Topics: Animals; Carbohydrate Conformation; Carcinoma; Clone Cells; Collagen; Fibronectins; Heparin; Heparitin Sulfate; Immune Sera; Immunohistochemistry; Lung Neoplasms; Membrane Glycoproteins; Mice; Protein Binding; Proteoglycans; Stromal Cells; Tumor Cells, Cultured

A routine procedure has been developed for the isolation and maintenance in culture of human ovarian carcinoma cells derived from biopsy specimens. Cell attachment, plating efficiency and initial outgrowth were greatly improved by seeding the cells on a basement-membrane-like extracellular matrix (ECM) deposited by cultured corneal endothelial cells. These effects were most significant in serum-free conditions which markedly reduced the rate of cell attachment and growth on regular tissue culture plastic. In 60-80% of the cases and regardless of the patient's age, cells cultured on ECM in the absence of serum divided actively and formed a tightly packed epithelial cell monolayer. Fibroblast overgrowth and cell detachment often occurred on ECM in the presence of serum. Incubation of the human ovarian carcinoma cells with sulfate-labelled ECM, resulted in the release of heparan sulfate degradation fragments, 4- to 7-fold smaller than intact heparan sulfate side chains. This degradation was brought about by endoglycosidase (heparanase) activity expressed to a higher extent by cells that were first maintained in primary cultures as compared with cell aggregates taken directly from the biopsy specimen. In most cases, cells derived from metastatic tumors expressed a higher heparanase activity than cells from the primary ovarian tumor. This result corroborates previous studies, performed with cell lines, on the possible involvement of heparanase in tumor cell invasion and metastasis.

Topics: Autoradiography; Biopsy; Carcinoma; Chondroitin Sulfate Proteoglycans; Cytological Techniques; Extracellular Matrix; Female; Gene Expression Regulation, Enzymologic; Glucuronidase; Glycoside Hydrolases; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Neoplasm Metastasis; Ovarian Neoplasms; Tumor Cells, Cultured

Human colon carcinoma cells synthesize a high-molecular-weight heparan sulfate proteoglycan which is localized at the cell surface. In this study we have performed a series of immunoprecipitation and pulse-chase experiments associated with various pharmacological agents that interfere with the synthesis and post-translational modification of the proteoglycan. We demonstrate that colon carcinoma cells synthesize the heparan sulfate proteoglycan from a 400-kDa precursor protein that is immunologically related to the Engelbreth-Holm-Swarm (EHS) tumor cell proteoglycan. The cells contain a large pool of precursor protein with a half-life of about 75 min. Most of the precursor protein receives heparan sulfate side chains and is then transported to the cell surface and released into the medium. A portion of the precursor pool, however, does not receive heparan sulfate chains but is secreted into the medium. The glycosylation and subsequent secretion of the 400-kDa precursor protein was inhibited by NH4Cl and even more by monensin, indicating that the transit of precursor from the rough endoplasmic reticulum to the cell surface occurred through the Golgi complex and acidic compartments. The existence of a sizable pool of precursor protein was confirmed by additional experiments using cycloheximide and xyloside. These experiments showed that the half-life of the precursor protein was also 75 min and that stimulation of heparan sulfate synthesis by xyloside was greatly enhanced (about 12-fold) after new protein core synthesis was blocked by cycloheximide. Although the structural models proposed for the EHS and colon carcinoma heparan sulfate proteoglycans differ, the observation that they are derived from a precursor protein with dimensional and immunological similarities suggests that they may be genetically related.

Topics: Ammonium Chloride; Blotting, Western; Carcinoma; Cell Line; Chondroitin Sulfate Proteoglycans; Colonic Neoplasms; Cycloheximide; Glycosaminoglycans; Glycosides; Heparitin Sulfate; Humans; Monensin; Polysaccharide-Lyases; Precipitin Tests; Protein Precursors; Protein Processing, Post-Translational; Proteoglycans; Trypsin

Differential cell adhesion has been proposed to play a role in organ-specific tumor metastasis. To further explore this hypothesis, we have employed a Lewis lung carcinoma cell line and 2 variants that differ in their ability to metastasize to lung and liver. The three cell lines were tested for their ability to adhere to defined extracellular matrix components that had been previously adsorbed to nylon membranes. Our results demonstrate that the parental cell line adheres preferentially to fibronectin relative to all other adhesion molecules tested. The lung colonizing variant, M27, adheres well to fibronectin and also to type V collagen but adheres poorly to laminin, to types I and VI collagen or to heparan sulfate. In contrast, the liver colonizing H59 cell line was highly adherent to laminin as well as to fibronectin but did not adhere to heparan sulfate or to any of the collagen types tested. These results demonstrate that three related cell lines with differing metastatic specificities have marked differences in their abilities to bind to defined matrix molecules. Such differences may play a role in the preferential localization to specific organ beds in vivo.

Topics: Animals; Carcinoma; Cell Adhesion; Collagen; Extracellular Matrix; Fibronectins; Heparitin Sulfate; Kinetics; Laminin; Liver Neoplasms; Lung Neoplasms; Mice; Neoplasm Metastasis

Using a modified papain digestion cetylpyridinium salt precipitation method, glycosaminoglycans were isolated from 21 mesotheliomas, 34 primary lung carcinomas, 12 carcinomas of other sites, and 7 soft tissue sarcomas. Qualitatively, hyaluronic acid (HA) was present in 20 of 21 mesotheliomas, about half of the primary lung adenocarcinomas, and all of the soft tissue sarcomas. On the average, HA constituted 45% of the total glycosaminoglycans in the mesotheliomas and 28% of the total in the lung cancers. Quantitatively, mesotheliomas contained statistically greater amounts (mean value, 0.74 mg/g) of HA than primary lung adenocarcinomas (mean value, 0.08 mg/g), but were not statistically different from soft tissue sarcomas (mean value, 2.01 mg/g) or primary ovarian serous neoplasms (mean value, 0.92 mg/g). The study concludes that, contrary to previous reports, HA is neither the sole nor the predominant glycosaminoglycan in most mesotheliomas, but, given the proper clinical and histologic setting, the finding of sufficiently high levels (greater than 0.4 mg/g dry tissue extract) supports the diagnosis of mesothelioma when the alternative diagnosis is primary adenocarcinoma of lung.

Topics: Adenocarcinoma; Carcinoma; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Sarcoma