chondroitin-sulfates and Colonic-Neoplasms

Chondroitin sulfate (CS), mainly present in the cartilage and bone of animals, is known as a potential food-derived bioactive that has several biological functions, such as anti-arthritic and anti-inflammatory activity. Sturgeon (

Topics: Animals; Apoptosis; Cartilage; Cell Proliferation; China; Chondroitin Sulfates; Colonic Neoplasms; Dose-Response Relationship, Drug; Fishes; HCT116 Cells; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Signal Transduction

We examined whether chondroitin sulfates (CSs) exert inhibitory effects on heparanase (Hpse), the sole endoglycosidase that cleaves heparan sulfate (HS) and heparin, which also stimulates chemokine production. Hpse-mediated degradation of HS was suppressed in the presence of glycosaminoglycans derived from a squid cartilage and mouse bone marrow-derived mast cells, including the E unit of CS. Pretreatment of the chondroitin sulfate E (CS-E) with chondroitinase ABC abolished the inhibitory effect. Recombinant proteins that mimic pro-form and mature-form Hpse bound to the immobilized CS-E. Cellular responses as a result of Hpse-mediated binding, namely, uptake of Hpse by mast cells and Hpse-induced release of chemokine CCL2 from colon carcinoma cells, were also blocked by the CS-E. CS-E may regulate endogenous Hpse-mediated cellular functions by inhibiting enzymatic activity and binding to the cell surface.

Topics: Animals; Bone Marrow Cells; Cartilage; Cell Line; Cell Line, Tumor; Cell Membrane; Chemokines; Chondroitin Sulfates; Colon; Colonic Neoplasms; Decapodiformes; Glucuronidase; Glycosaminoglycans; Heparitin Sulfate; Humans; Mast Cells; Mice; Recombinant Proteins

Targeted delivery of chemotherapeutic drugs to tumors is a major challenge in colon cancer chemotherapy. To overcome this bottleneck, we loaded camptothecin (CPT) into polymeric nanoparticles (NPs), and further functionalized their surface with chondroitin sulfate (CS). The resulting CS-CPT-NPs had a desirable hydrodynamic diameter (289 nm), narrow particle size distribution (polydispersity index = 0.192) and neutral surface charge. Furthermore, in vitro experiments revealed that the surface functionalization of CS endowed NPs with the capacity of colon cancer-targeted drug delivery, and significantly improved the anti-colon cancer activities and pro-apoptosis effects against colon cancer cells. Strikingly, treatment of colon tumor-bearing mice with different NPs clearly indicated that CS-CPT-NPs showed much better therapeutic outcomes than non-targeted NPs and no systemic toxicity. Taken together, these results demonstrated the promising potential of CS-CPT-NP as an effective drug delivery system for colon cancer-targeted chemotherapy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Camptothecin; Cell Proliferation; Cell Survival; Chondroitin Sulfates; Colonic Neoplasms; Drug Delivery Systems; Drug Screening Assays, Antitumor; Humans; Hydrodynamics; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasms, Experimental; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Surface Properties; Tumor Cells, Cultured

Self-assembled nanoparticles using the biopolymers chitosan (CH) and chondroitin sulfate (CS) were developed to improve the biological activity of anthocyanin (ACN). The 86.32 ± 0.15% (w/w) of ACN was incorporated into ACN/CH/CS nanoparticles, with the particle size of 350.1 ± 0.99 nm in diameter (i.d.) and 42.55 ± 0.54 in zeta potential (mV). Morphological study and thermogravimetric analysis suggested that the ACN/CH/CS nanoparticles exhibited heterogeneous morphology and high thermal stability. Significant increases in apoptosis by 12.1% and 35.1% were observed with 0.05 mg/ml ACN and ACN/CH/CS nanoparticles in the HCT-116 cell line, indicating that the nanoparticle system led to significant increase in apoptosis (p < 0.05). Structural changes in mitochondria caused by ACN/CH/CS nanoparticles indicated that the nanoparticles had negative impacts on mitochondria. These results showed that nanoparticles could potentially be used as a carrier system to improve the efficacy of ACN.

Topics: Anthocyanins; Antineoplastic Agents; Apoptosis; Chitosan; Chondroitin Sulfates; Colonic Neoplasms; HCT116 Cells; Humans; Nanoparticles; Oryza; Particle Size

Chemoresistance is one of the major barriers for tumor chemotherapy. It is clinically known that chemoresistance increases during tumor progression. Additionally, the extracellular matrix (ECM) is also remodeled during tumor progression. However, it remains unclear how ECM remodeling contributes to chemoresistance acquisition. Recently, it has been reported that epithelial-mesenchymal transition (EMT) contributes to chemoresistance acquisition. Here, how ECM remodeling contributes to 5-fluorouracil (5-FU) resistance acquisition was investigated from the viewpoints of EMT using in vitro ECM models mimicking native ECM in colorectal tumor tissue at three different malignant levels. 5-FU partially induced EMT and increased ABCB1 in colorectal HT-29 cells via TGF-β signaling (an invasive tumor cell model). When HT-29 cells were cultured on an ECM model (high malignant matrices) mimicking native ECM in highly malignant tumor tissues, the cells facilitated TGF-β-induced EMT and increased ABCB1 upregulation compared with that of other ECM models mimicking the low malignant level and normal tissues. High malignant matrices contained more chondroitin sulfate (CS) chains than those of other ECM models. Finally, CS chain-reduced high malignant matrices could not facilitate ABCB1 upregulation and TGF-β-induced EMT. These results demonstrated that ECM remodeling during tumor progression increased CS chains to facilitate EMT and ABCB1 upregulation, contributing to chemoresistance acquisition.

Topics: Cell Line, Tumor; Cell Proliferation; Chondroitin Sulfates; Colonic Neoplasms; Colorectal Neoplasms; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Extracellular Matrix; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Signal Transduction; Up-Regulation

Glycans play a critical role in physiological and pathological processes through interaction with a variety of ligands. Altered expression and dysregulation of these molecules can cause aberrant cellular function such as malignancy. Glycomics provide information of the structure and function of glycans, glycolipids, and glycoproteins such as proteoglycans, and may help to predict cancer development and progression as biomarkers. In this report, we compared the expression of proteoglycans, the content and structure of glycosaminoglycans and glycolipids between patient-matched normal and cancer tissues obtained from colon cancer patients. Tumor-related proteoglycans, glypican-3, and syndecan-1 showed downregulation in cancer tissues compared to normal tissues. In cancer tissue, the total amount of chondroitin sulfate (CS)/dermatan sulfate and heparan sulfate were lower and, interestingly, the level of disaccharide units of both 4S6S (CS-E) and 6S (CS-C) were higher compared to normal tissue. Also, overall lipids including glycolipids, a major glycomics target, were analyzed by hydrophilic interaction liquid chromatography mass spectrometry. Increase of lyso-phosphatidylcholine (phospholipid), sphingomyelin (sphigolipid), and four types of glycolipids (glucosylceramide, lactosylceramide, monosialic acid ganglioside, and globoside 4) in cancer tissue showed the possibility as potential biomarkers in colon cancer. While requiring the need for careful interpretation, this type of broad investigation gives us a better understanding of pathophysiological roles on glycosaminoglycans and glycolipids and might be a powerful tool for colon cancer diagnosis.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, CD; Biomarkers; Carbohydrate Sequence; Case-Control Studies; Chondroitin Sulfates; Colonic Neoplasms; Dermatan Sulfate; Female; Gangliosides; Gene Expression Regulation, Neoplastic; Globosides; Glucosylceramides; Glypicans; Heparitin Sulfate; Humans; Lactosylceramides; Lysophosphatidylcholines; Male; Middle Aged; Molecular Sequence Data; Sphingomyelins; Syndecan-1

Proteoglycans (PGs), glycosaminoglycans (GAGs) and hyaluronan as a free GAG, have unique structural characteristics which enable them via specific interactions with matrix proteins and cell surface receptors to regulate key tumor cell functions and thus to affect cancer growth and progression. This article explores the many layers of interdependent signaling among transformed colon epithelial cells, neighboring stromal cells and their respective PGs / GAGs components along the insidious and often deadly route of colon cancer progression. Specifically addressed is the altered deposition of PGs / GAGs by colon cancer cells; the effects of these malignant cells on gene expression and biosynthesis of PGs / GAGs of the surrounding stromal cells and the signaling pathways involved, with the utmost goal to highlight potential therapeutic targets in the rapidly developing field of glycan-based therapy.

Topics: Animals; Antineoplastic Agents; Chondroitin Sulfates; Colon; Colonic Neoplasms; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Molecular Targeted Therapy; Proteoglycans; Signal Transduction

Polarized epithelial cells like Madin-Darby canine kidney (MDCK) and CaCo-2 cells synthesize and secrete proteoglycans (PGs), mostly of heparan sulphate (HS) type in direction of the basal extracellular matrix, but also some in the apical direction. MDCK cells possess the capacity to synthesize chondroitin sulphate (CS) PGs that are mainly secreted into the apical medium, a process that is enhanced in the presence of hexyl-beta-D: -xyloside. We have now tested the capacity of several xylosides to enhance glycosaminoglycan (GAG) chain secretion from the human colon carcinoma cell line CaCo-2 in the differentiated and non-differentiated state. In these cells, benzyl-beta-D: -xyloside was a potent initiator of CS chains, which for these cells were predominantly secreted into the basolateral medium. Xylosides with other aglycone groups mediated only minor changes in GAG secretion. Although benzyl-beta-D: -xyloside stimulated the basolateral CS-GAG secretion in both differentiated and undifferentiated CaCo-2 cells, basolateral secretion of trypsin-like activity was dramatically enhanced in undifferentiated cells, but not significantly altered in differentiated cells.

Topics: Caco-2 Cells; Cell Differentiation; Cell Polarity; Chondroitin Sulfates; Colonic Neoplasms; Culture Media, Conditioned; Glycosaminoglycans; Glycosides; Humans; Immunoprecipitation; Proteoglycans; Trypsin

The cancer microenvironment and the interactions between cancer and surrounding tissue cells are thought to play a pivotal role in tumor development and progression. Glycosaminoglycans (GAGs)/proteoglycans (PGs) are major constituents of the extracellular matrix, the composition of which may affect various cellular functions. In the present study, the effects of GAGs on the proliferation of HT29, SW1116, and HCT116 human colon cancer cell lines were examined using exogenously added GAGs, an inhibitor of endogenous GAG sulfation and specific glycosidase digestions. Our results demonstrate that colon cancer cell growth was exclusively stimulated by exogenously added heparin and insensitive to endogenous GAGs/PGs production, in a sulfation pattern-related manner. Treatment of the tested cell lines with the FGF-2 neutralizing antibody showed that the stimulatory effect of heparin on the cells' growth was not FGF-2-dependent. Responsiveness of colon cancer cell lines to exogenous heparin/heparan sulfate may play a role in their growth and metastasis.

Topics: Blotting, Western; Cell Proliferation; Chondroitin Sulfates; Colonic Neoplasms; Dermatan Sulfate; Fibrinolytic Agents; Fibroblast Growth Factor 2; Heparin; Heparitin Sulfate; Humans; Hyaluronic Acid; Receptors, Fibroblast Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfates; Tumor Cells, Cultured

Interactions of tumour and stromal cells influence tumour cell proliferation and differentiation, stromal cell phenotypic transdifferentiation and secretion of extracellular matrix (ECM) components. In this study, we established a monolayer and a three-dimensional cell-to-cell interaction model between canine mammary stromal cells and human colonic carcinoma cell lines (Caco-2 and HT-29) to investigate mutual paracrine effects of tumour cells and stromal cells on (i) tumour cell differentiation, (ii) production of ECM components and (iii) phenotypic transdifferentiation of stromal cells. We showed that when Caco-2 or HT-29 cells are cultured in collagen gels, they form a few small solid cell clusters with no lumina, but when cocultured with stromal cells, the tumour cells formed glandular structures with central lumina. This fibroblast-induced organization and differentiation of Caco-2 cells (not HT-29 cells) appeared to be mediated by transforming growth factor-beta (TGF-beta). Culturing of stromal cells, Caco-2 cells or HT-29 cells alone in both monolayers and gels resulted in weak tenascin-C expression in stromal cells and HT-29 cells and no expression in the Caco-2 cells. Coculturing of stromal cells with tumour cells resulted in increased tenascin-C expression in the stromal cells and HT-29 cells and induced expression of tenascin-C in the Caco-2 cells. This induction and increased expression of tenascin-C appeared to be mediated by TGF-beta. Culturing of stromal cells, Caco-2 cells or HT-29 cells alone on monolayers and in gels resulted in a weak expression of chondroitin sulfate (CS), chondroitin-6-sulfate (C-6-S) and versican in stromal cells and no expression in Caco-2 and HT-29 cells. Coculturing of stromal cells with tumour cells on monolayers and in gels resulted in increased CS, C-6-S and versican expression in stromal cells. This tumour cell-induced expression of CS, C-6-S and versican appeared to be mediated by TGF-beta and platelet-derived growth factor (PDGF). Coculturing of Caco-2 and HT-29 and stromal cells promoted the transdifferentiation of stromal cells into myofibroblasts, and this appeared to be mediated by TGF-beta. These results suggest that TGF-beta and PDGF are part of a paracrine system involved in stromal-epithelial cell interaction important in stromal cell differentiation and ECM component production.

Topics: Actins; Animals; Caco-2 Cells; Cell Differentiation; Cell Transformation, Neoplastic; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Coculture Techniques; Colonic Neoplasms; Dogs; Extracellular Matrix; Fibroblasts; HT29 Cells; Humans; Immunohistochemistry; Lectins, C-Type; Muscle, Smooth; Neoplasm Proteins; Phenotype; Stromal Cells; Tenascin; Versicans

Changes in the production and structure of glycosaminoglycans and proteoglycans have been reported in many neoplastic tissues, and versican and hyaluronan (extracellular matrix components) are frequently increased in tumours and promote tumour progression. The distribution of chondroitin sulphate, versican and hyaluronan in normal canine colonic wall (n=10), and normal colonic lymph nodes (n=10), colonic adenomas (n=22), colonic adenocarcinomas (n=28), colonic undifferentiated carcinomas (n=7), and colonic lymph node metastases (n=8), was examined, with antibodies against chondroitin sulphate and versican, and a specific biotinylated probe for hyaluronan. The epithelial cells of the normal colonic mucosa were negative for all three substances, whereas the stromal tissue and lamina propria were moderately positive for chondroitin sulphate and hyaluronan, and weakly positive for versican. Chondroitin sulphate expression was increased in adenomas and carcinomas. However, there was no significant correlation between grade of tumour and degree of chondroitin sulphate expression. Versican expression was increased in the peritumoral stroma of adenocarcinomas and reduced in adenomas. A significant correlation was observed between grade of tumour and degree of versican expression. In 13 adenocarcinomas and undifferentiated carcinomas with invasion into all layers of the colorectum, the intensity of stromal versican expression was significantly related to the depth of invasion; the intensity was increased in the stroma of tumour islands in deep layers of the colonic wall. Unlike versican expression, hyaluronan expression was increased in the stromal tissue of both adenomas and carcinomas. However, the degree of stromal hyaluronan expression was unrelated to tumour grade and depth of tumour invasion. Hyaluronan was also expressed in the membrane and in the cytoplasm of tumour cells in 3/22 (14%) adenomas, 18/28 (64%) adenocarcinomas and 2/7 (29%) undifferentiated carcinomas. These results suggest that altered levels of both versican and hyaluronan in canine colonic tumours affect tumour progression.

Topics: Adenoma; Animals; Biomarkers, Tumor; Carcinoma; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Colonic Neoplasms; Dog Diseases; Dogs; Hyaluronic Acid; Immunoenzyme Techniques; Lectins, C-Type; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness; Versicans

In order to screen out an optimum complex for reducing the nephrotoxicity of cisplatin (CDDP), we investigated and compared CDDP-chondroitin sulfate complexes to CDDP in terms of in vivo pharmacokinetics and in vitro cytotoxicity. The polymeric carriers used in the study were chondroitin sulfate A (CSA, 4-sulfate) with mean molecular weights of 10 kDa (CSA-1) and 23 kDa (CSA-2), and chondroitin sulfate C (CSC, 6-sulfate) with mean molecular weights of 8 kDa (CSC-1) and 25 kDa (CSC-2). The resultant complexes (CDDP-CSA-1, CDDP-CSA-2, CDDP-CSC-1 and CDDP-CSC-2) were administered intravenously to rats. The obtained plasma concentration-time curves during the 3 h period studied for all complexes are biphasic. The plasma dispositions of complexes were dependent on the molecular sizes with urinary excretion as main elimination pathway. CDDP-CSA-1 and CDDP-CSC-1 were unable to effectively increase the plasma retention of platinum due to rapid renal excretion. Furthermore, CDDP-CSA-1 disappeared from plasma more quickly than CDDP-CSC-1. CDDP-CSA-2 and CDDP-CSC-2, with similar urinary excretion as CDDP, gave rise to approximately five and four-fold increase in AUC(0-3 h) values, respectively, than that was achieved with native CDDP treatment. Biodistribution was compared between CDDP-CSA-2 and CDDP-CSC-2. Both complexes effectively suppressed the extensive distribution of CDDP into most tissues, especially kidney. However, CDDP-CSC-2 showed less reduction effect than CDDP-CSA-2. In addition, a significantly higher accumulation in tumor tissue was found with the administration of CDDP-CSA-2 than CDDP. Moreover, CSA complexes displayed an IC(50) of 6 microM Pt-equivalents against SW4800 human colon cancer cells, similar to that of CDDP, whereas CSC complexes were less active than CDDP. These studies indicate that the complex prepared with CSA, which is greater than 20 kDa of molecular size, is superior to that of CSC, exhibiting improved pharmacokinetics and similar pharmacological activity to the native drug.

Topics: Animals; Antineoplastic Agents; Cell Survival; Chondroitin Sulfates; Cisplatin; Colonic Neoplasms; Drug Carriers; Humans; Inhibitory Concentration 50; Male; Mice; Mice, Inbred Strains; Molecular Weight; Neoplasm Transplantation; Rats; Rats, Wistar; Sarcoma 180; Tissue Distribution; Tumor Cells, Cultured

Mouse colon carcinoma cell line colon 38 was used to investigate migratory factor for fibroblasts because marked fibrotic tissue was associated with these cells growing at transplanted sites and liver metastases in vivo. Migration-inducing activity was detected in the serum-free culture supernatants of colon 38 cells, as shown by the Boyden chamber assays using NIH3T3 cells as target cells. The active substance was partially purified by a combination of anion-exchange, hydrophobic, and gel-permeation chromatography. An approximate relative molecular mass of the active substance was estimated to be between 100,000 and 400,000, judging from the eluting position in the gel-permeation chromatography. The migratory activity in the partially purified preparation was removed by incubation with beads coated with an anti-mouse fibronectin antibody. NIH3T3 cells incubated in the presence of culture supernatants of colon 38 cells exhibited higher growth rate, organized actin filaments, and increased chondroitin sulfate and hyaluronan. Fibronectin did not elicit such effects and partially purified migratory factor showed relatively low activity in these regards. Thus, colon 38 cells seem to secrete fibronectin and other soluble substances, which induce tumor stroma formation through migration and activation of host fibroblasts.

Topics: 3T3 Cells; Actins; Animals; Blotting, Western; Cell Division; Cell Movement; Chondroitin Sulfates; Chromatography, Gel; Chromatography, Ion Exchange; Colonic Neoplasms; Culture Media, Conditioned; Culture Media, Serum-Free; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Fibronectins; Hyaluronic Acid; Immunohistochemistry; Mice; Precipitin Tests; Time Factors; Tumor Cells, Cultured

Binding studies with 125I-Tyr labelled hyaluronan (HA) on a cultured rat colon cancer cell line were performed to characterize the association of HA to tumour cells in vitro. Results show a specific and saturable binding (Kd=1.36 nM) which indicates the presence of an HA binding receptor on the tumour cells. There is a specific constant increase of cell-associated HA over time, which indicates that HA is specifically taken up by the cells through endocytosis. The binding of 125I-Tyr labelled HA was more effectively inhibited by unlabelled HA of high MW in relation to low MW species of the polysaccharide indicating that the receptor binds HA of high MW with greater affinity than low MW species. In competition experiments, the HA-binding could not be inhibited by other polysaccharides such as chondroitin sulphate and heparin. Nor could ligands for scavenger receptors and antibodies directed towards ICAM-1, CD 44 and RHAMM (Receptor for HA Mediated Motility) significantly inhibit the association of HA to tumour cells.

Topics: Animals; Antibodies; Chondroitin Sulfates; Colonic Neoplasms; Dextran Sulfate; Endothelium; Extracellular Matrix Proteins; Hyaluronan Receptors; Hyaluronic Acid; Intercellular Adhesion Molecule-1; Liver; Mice; Rats; Rats, Wistar; Tumor Cells, Cultured

To follow the biodistribution of exogenous hyaluronan in tumor-bearing animals, a total of seventeen inbred rats with hepatic metastases from a colonic adenocarcinoma received 125I-labelled hyaluronan by intravenous injections. Group I received only labeled hyaluronan (25 microg), whereas group II received 2.5 mg chondroitin sulphate prior to labeled hyaluronan, to block receptor uptake in normal liver endothelial cells. Animals in group III received intravenous, as well as intraperitoneal chondroitin sulphate (2.5 mg), to see if a better and prolonged blocking could be achieved. Radioactivity was visualized by whole body autoradiography, using phosphorimaging and the average radioactivity determined as phosphoimaging density units of the total area of hepatic metastases, normal liver, and skeletal muscle by computer-based image analysis. At 5 h, tumors in groups II and III showed higher uptake (4.8+/-1.8, P = .01 and 3.6+/-1.1, P = .01, respectively), in comparison to group I (1.8+/-0.6), and the mean normal liver/tumor concentration ratio was reduced from 21.4+/-10.1 in group I to 5.7+/-2.7 in group II and 3.5+/-1.1 in group III (P = .008 and P = .01, respectively). Our study shows that hyaluronan targets liver metastases of a colon adenocarcinoma. Furthermore, chondroitin sulphate pretreatment increases tumor uptake, while uptake at normal receptor sites is significantly reduced. The results also suggest that after blocking of normal hyaluronan/chondroitin sulphate receptors in healthy tissue, hyaluronan may be used to deliver drugs to specific hyaluronan receptor-positive sites of pathology.

Topics: Adenocarcinoma; Animals; Autoradiography; Chondroitin Sulfates; Colonic Neoplasms; Female; Hyaluronan Receptors; Hyaluronic Acid; Image Processing, Computer-Assisted; Iodine Radioisotopes; Liver Neoplasms, Experimental; Neoplasm Metastasis; Rats; Rats, Wistar; Tissue Distribution; Tumor Cells, Cultured

In order to elucidate the gross composition of fibrous stroma and to better understand the obstructive nature of advanced human colonic cancers the extracellular matrix components of its stroma were analyzed immunohistologically, emphasizing the process of fibrosis and possible tissue constriction. Collagenous material, identified by Masson's trichrome stain, was distributed mainly in the invasive area, where type I and III collagens and chondroitin 4-sulfate stained intensely in the periacinar area, and further, fibronectin stained. Conversely, in the invasive area away from tumor acini type III collagen stained weakly and fibronectin not at all. Type V collagen and myofibroblasts stained in the periacinar area and did not stain in the invasive area away from tumor acini, the findings of myofibroblasts being prominent in cases with obstructive type carcinomas. In conclusion, the invasive area, especially the periacinar area, displayed signs of active ongoing fibrosis and tissue contraction, which may be responsible for the genesis of obstructing type colonic carcinomas.

Topics: Adenocarcinoma; Chondroitin Sulfates; Collagen; Colon; Colonic Neoplasms; Extracellular Matrix; Fibronectins; Fibrosis; Humans; Immunoenzyme Techniques

A transplantable colorectal adenocarcinoma and the normal colonic mucosa derived from rats of ACI/N strain were digested with pronase, and the glycosaminoglycan fractions were obtained by fractionation with cetylpyridinium chloride. The glycosaminoglycan fraction derived from the adenocarcinoma contained substantial amounts of chondroitin sulfate A/C, dermatan sulfate, heparan sulfate, and hyaluronic acid, whereas chondroitin sulfate A/C and dermatan sulfate were undetectable in that derived from the normal colonic mucosa. An increment in the heparan sulfate content was also apparent in the adenocarcinoma, while the level of hyaluronic acid appeared to be unchanged. Analyses of the extract of the tumor tissue with 5mM ethylenediaminetetraacetate (pH 7.0) indicated that heparan sulfate was present largely, if not completely, in the form of proteoglycan.

Topics: Adenocarcinoma; Animals; Chemical Fractionation; Chondroitin Sulfates; Colon; Colonic Neoplasms; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Mucous Membrane; Neoplasms, Experimental; Rats; Rats, Inbred ACI; Rectal Neoplasms

The glycosaminoglycans from normal colonic mucosa and colons with a variety of inflammatory diseases, as well as benign and malignant neoplasms were analyzed. Normal colonic mucosa contains predominantly chondroitin sulfates and dermatan sulfate. Increases in the levels of hyaluronic acid and heparan sulfate, as well as substantial increases in the amount of total glycosaminoglycans were characteristic of invasive colonic adenocarcinoma. Lesser elevations in the amount of total glycosaminoglycans and hyaluronic acid and heparan sulfate were present in neonatal colonic mucosa, villous adenoma, ulcerative colitis, and mucosa adjacent to carcinoma. The degree of elevation was proportional to the dysplastic potential. Since dysplastic lesions have scant connective tissue, the epithelial component of colonic neoplasms may contribute to these neoplasm-related alterations in glycosaminoglycan composition.

Topics: Adenocarcinoma; Adult; Aged; Chondroitin Sulfates; Colitis; Colon; Colonic Neoplasms; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Intestinal Mucosa; Male; Middle Aged

Normal, transitional, and carcinoma areas of five colons resected for carcinoma were examined morphologically, histochemically, and biochemically. The transitional area contained a larger amount of non-sulphated acid mucin than the normal mucosa as verified histochemically. Normal mucosa contained mainly sulphated mucin. The hexosamine-containing macromolecules present in different areas were isolated and characterized. They were divided into the following groups: 1) acid glycosaminoglycans, 2) high-molecular-weight glycopeptides, and 3) low-molecular weight glycopeptides. The concentration of the total hexosamine-containing material was in the carcinoma area twice as high as in normal areas. Acid glycosaminoglycans were identified as hyaluronate, heparan sulphate, dermatan sulphate, and chondroitin 4-(6)-sulphate. Their concentraitons were found to increase from normal to transitional and from transitional to carcinoma areas. The high-molecular-weight glycopeptide was composed of fucose, galactose, glucosamine, galactosamine, sialic acid, and variable amounts of sulphate. The sulphation degree of the glycopeptide was higher in normal mucosa than in transitional or carcinoma areas: The low-molecular-weight glycopeptides consisted of about a half of the total hexosamine-containing substances. The concentration of saline-insoluble fraction of the low-molecular-weight glycopeptides was in transitional areas about two times, and in carcinoma areas about four times, higher than in normal mucosa.

Topics: Adenocarcinoma; Chondroitin Sulfates; Colonic Neoplasms; Dermatan Sulfate; Fucose; Galactosamine; Galactose; Glucosamine; Glycopeptides; Glycosaminoglycans; Heparitin Sulfate; Hexosamines; Histocytochemistry; Humans; Hyaluronic Acid; Intestinal Mucosa; Macromolecular Substances; Molecular Weight; Mucins; Sialic Acids; Sulfates