concanavalin-a and Precancerous-Conditions

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

Topics: Adult; Aged; alpha 1-Antitrypsin; Apolipoprotein A-I; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Chromatography, Affinity; Chromatography, Agarose; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Glycosylation; Humans; Male; Mass Spectrometry; Middle Aged; Mouth Neoplasms; Plant Lectins; Precancerous Conditions; Squamous Cell Carcinoma of Head and Neck

Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow Transplantation; Carrageenan; Chondrocytes; Concanavalin A; Drug Eruptions; Ear Diseases; Ear Neoplasms; Ear, External; Epidermis; Epithelium; Female; Graft vs Host Reaction; Hyperplasia; Hypertrophy; Indomethacin; Keratinocytes; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Inbred ICR; Mice, SCID; Moloney murine sarcoma virus; Precancerous Conditions; Sarcoma, Experimental; Transplantation, Heterotopic

Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors arise from the proximal tubules. In the present study, lectin-binding characteristics and cytokeratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from which tumors arise. Lectin-binding histochemistry has been used as a marker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-molecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubules by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Ricinus communis (RCA-1), and Triticum vulgare and to the distal tubules by Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin binding and cytokeratin staining patterns of rat hereditary renal cell carcinoma, adenoma and the preneoplastic lesions of atypical tubules and hyperplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principally the proximal tubule.

Topics: Adenoma; Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Concanavalin A; Histocytochemistry; Hyperplasia; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lectins; Male; Plant Lectins; Precancerous Conditions; Rats; Rodent Diseases; Wheat Germ Agglutinins

Squamous metaplasia of tracheal mucosa, putative preneoplastic lesions, involves replacement of normal mucociliary epithelium with epidermoid lesions. Alterations in cell differentiation and neoplasia accompany changes in glycoconjugates at the plasma membrane. Lectins which bind to specific cell surface glycoconjugates are used to elucidate such alterations. We have used peanut agglutinin (PNA) and concanavalin A (Con A) as specific molecular probes to elucidate cell specific alterations in the development and progression of squamous metaplasia in the hamster tracheal explants induced by benzo[a]pyrene (BP), a component of cigarette smoke. The tracheal explants were cultured in serum-free chemically defined medium and treated with BP (7.5 micrograms/ml) for up to 15 days. At this time, 80-90% of the carcinogen treated explants exhibited epidermoid lesions at various stages of development. The untreated control explants maintained normal pseudostratified epithelium. In these explants, PNA and Con A exhibited moderate reaction in the cytoplasm of luminal mucociliary cells; the basal cells showed no reaction. In early metaplastic lesions PNA and Con A stained only the cytoplasm of luminal cells; the metaplastic cells along the basal lamina were negative. In well-developed lesions, in which the luminal mucociliary layer was still intact overlying the lesions, the metaplastic epithelium remained unreactive with the lectins. In highly advanced lesions exhibiting cornification, and in which the mucociliary layer was sloughed, the metaplastic lesions showed strong reaction with both the lectins. The reaction was limited mainly to the plasma membrane of the metaplastic cells. These results show that induction and progression of the BP induced lesions accompany dynamic cell specific alterations in glycoconjugates. The epidermoid lesions acquire glycoconjugates rich in beta-D-galactose and D-mannose. These results are also consistent with the basal cell origin of the metaplastic lesions.

Topics: Animals; Benzo(a)pyrene; Cell Membrane; Concanavalin A; Cricetinae; Culture Techniques; Glycoconjugates; Lectins; Mesocricetus; Metaplasia; Peanut Agglutinin; Precancerous Conditions; Trachea; Tracheal Neoplasms

Topics: Animals; Antibodies, Monoclonal; B-Lymphocytes; Concanavalin A; Female; Killer Cells, Natural; Lymphocyte Activation; Lymphoma; Male; Monkey Diseases; Papio; Precancerous Conditions; T-Lymphocytes; T-Lymphocytes, Regulatory

For the detection of cancerous and precancerous lesions in cervical cytopathology, the feasibility of a concanavalin A-peroxidase labeling procedure was tested and compared with the Papanicolaou method. To this end, the percentage of labeled flattened epithelial cells with a morphologically normal appearance present in cervical cell suspensions was determined. It was found that the mean labeling percentage of the control group was 71% (SD, 11%). The means for mild, moderate, and severe dysplasia groups were, respectively, 54% (SD, 19%), 48% (SD, 13%), and 44% (SD, 16%). The mean for the carcinoma in situ group was 32% (SD,11%), and for the squamous cell carcinoma group 16% (SD, 5%). It appeared that the labeling percentage gradually decreases with increasing atypia of the epithelium as confirmed by histological observation. A complete dissimilarity was found between healthy individuals and cancer patients. In a follow-up study it was found that the mean labeling percentage did not alter in cases of an unchanged stage of disease. A reestablishment of the normal concanavalin A-peroxidase labeling percentage often appeared once the cancerous or precancerous lesion was treated. In conclusion, the concanavalin A-peroxidase labeling method can be considered as a supplementary technique to the Papanicolaou method for the early detection of cervical cancer. It reduces the effect of sampling and screening errors of the Papanicolaou method, and it allows a more objective cytological diagnosis. In addition, it may possess prognostic significance.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Adhesion; Concanavalin A; Female; Horseradish Peroxidase; Humans; Precancerous Conditions; Uterine Cervical Neoplasms

The lectin, Concanavalin A(Con A) has been used to localize specific sugar residues (D-glucose, D-mannose and D-fructose) in premalignant lesions and squamous-cell carcinomas induced following cryosurgery of the mouse submandibular gland. The original Con A-horseradish peroxidase (HRP) technique as well as its combination with periodate oxidation and subsequent reduction by borohydrate were used to compare the epithelial elements during submandibular gland carcinogenesis. Granules in the granular convoluted tubule cells which were weakly reactive to the Con A-HRP method were not present in the premalignant duct like structures. The epithelium of premalignant lesions, duct-like structures, multicystic lesions, and squamous-cell carcinomas were positive for the cell-surface and intercellular substances; and basement membranes and stromal fibers were also positive. The results indicated that throughout malignant transformation of the ductal segments, premalignant epithelia lost Con A-HRP-staining granules and that Con A-binding patterns in induced squamous-cell carcinomas were similar to those found in squamous-cell epithelium.

Topics: Animals; Carcinoma, Squamous Cell; Concanavalin A; Male; Mannose; Methylmannosides; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Precancerous Conditions; Receptors, Concanavalin A; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

Three cell surface parameters of epidermal cells have been studied by immunofluorescence, pemphigus antigens, concanavalin-A binding sugars, and beta 2 microglobulin. Biopsy specimens were taken from a total of 59 patients with psoriasis, seborrheic and solar keratosis, squamous cell carcinoma, and basal cell epithelioma. We found a loss of demonstrability of all parameters in dedifferentiated tumors or tumor areas in squamous cell carcinoma, premonitory changes in solar keratosis, and no changes in seborrheic keratosis. In the psoriatic epidermis a granular redistribution of the cell surface parameters was occasionally observed in circumscribed areas of the epidermis. A selective loss of the demonstrability of beta 2 microglobulin was the prominent feature in basal cell epithelioma. Our findings demonstrate that the alterations of the cell surface differ in malignant and premalignant skin tumors, in basal cell epithelioma, and in benign psoriatic hyperplasia.

Topics: Antigens; beta 2-Microglobulin; Beta-Globulins; Binding Sites; Carcinoma, Squamous Cell; Concanavalin A; Fluorescent Antibody Technique; Humans; Keratosis; Pemphigus; Precancerous Conditions; Psoriasis; Skin Neoplasms

Saccharin is known to have a tumor-promoting effect on bladder cancer in rats, but its mechanism of action is unknown. We demonstrated that the increased agglutinability of isolated epithelial cells of the bladder in the presence of concanavalin A caused by a subcarcinogenic dose of bladder carcinogens disappeared shortly after the end of their administration. However, saccharin maintained the increased agglutinability when given continuously after administration of carcinogen. Moreover, the agglutinability of bladder cells previously exposed to a subcarcinogenic dose of bladder carcinogens increased again when saccharin was given after the agglutinability had disappeared completely.

Topics: Animals; Butylhydroxybutylnitrosamine; Cell Aggregation; Cell Membrane; Cocarcinogenesis; Concanavalin A; Diet; FANFT; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Strains; Saccharin; Urinary Bladder; Urinary Bladder Neoplasms

The hypertrophic duct epithelium of the pancreas, including the pyloric gland metaplasia, mucous cell hypertrophy and ductal papillary hyperplasia were studied clinico-pathologically and histochemically to examine their precancerous character. A total of 180 surgical and autopsy specimens (90 pancreata with cancer and 90 pancreata without cancer) were analysed. The overall incidence of these three types of hypertrophic epithelium in the pancreas cancer was much higher than that in the pancreas without cancer. These hypertrophic lesions appeared most frequently in the interlobular duct. The histochemical study revealed the presence of a new type of glycoprotein in these hypertrophic duct epithelia, however, this substance was not detected in the cancer cells nor in the normal epithelium. This suggests that these hypertrophic lesions may not be the precursors of cancer but rather the coexistent lesions of pancreas cancer.

Topics: Adult; Aged; Concanavalin A; Cytoplasm; Epithelium; Glycoproteins; Glycosaminoglycans; Histocytochemistry; Horseradish Peroxidase; Humans; Hypertrophy; Middle Aged; Mucoproteins; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Neoplasms; Precancerous Conditions; Staining and Labeling

The concanavalin A (Con A)-induced agglutinability of normal, preneoplastic, and neoplastic mouse mammary epithelial cells was examined. Cells freshly dissociated from normal mammary glands, hyperplastic alveolar nodules, or primary mammary adenocarcinomas by collagenase digestion in the presence of bovine serum albumin were strongly agglutinated by low concentrations of Con A. After short-term culture in vitro, however, cells from all three types of tissue were only weakly agglutinated by Con A, as measured by both suspension and hemadsorption assays. By comparison, cells of three established mammary tumor culture lines agglutinated strongly in the presence of the lectin. Treatment of the normal, preneoplastic, and neoplastic mammary cells in primary cultures with either trypsin or collagenase had little or no effect on their agglutinability, whereas hyaluronidase significantly increased their reactivity. Studies with fluorescein-tagged Con A indicated that all three cell types were capable of binding the lectin. The results were consistent with previous evidence suggesting that neoplastic transformation of mouse mammary epithelial cells is not manifested in vitro by several of the alterations in growth patterns, intercellular interactions, and surface properties that usually accompany transformation of fibroblastic cells.

Topics: Animals; Cells, Cultured; Concanavalin A; Female; Hemagglutination Tests; Hyaluronoglucosaminidase; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Precancerous Conditions; Receptors, Concanavalin A

N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), which is a potent, specific bladder carcinogen in rats, and its related compounds were orally administered to rats for 1 week. The bladder cells were isolated by the treatment with EDTA and sonication and they were subjected to agglutination assay by concanavalin A (Con A). Bladder cells obtained from rats treated with BBN, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) and N-butyl-N-(2-hydroxyethyl)nitrosamine (BHEN) were agglutination-positive, while those cells treated with N-tert-butyl-N-(4-hydroxybutyl)-nitrosamine (t-BBH) and N-butyl-N-(3-hydroxypropyl)nitrosamine (BHPN) were negative. Results obtained by this method were highly correlated with the known carcinogenicity of BBN and its analogues. Therefore, this method could be used for rapid screening of bladder carcinogens.

Topics: Animals; Butylhydroxybutylnitrosamine; Carcinogens; Cell Aggregation; Concanavalin A; Drug Evaluation, Preclinical; Humans; In Vitro Techniques; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Urinary Bladder; Urinary Bladder Neoplasms

Functional markers and growth behavior of abnormal hepatocytes at several stages of liver carcinogenesis were studied. Early lesions, i.e., hyperplastic foci and areas, did not accumulate iron in siderotic livers, had persistent glycogen stores, were not more agglutinable by concanavalin A, and were associated with alpha-fetoprotein secretion, but were not independent secretors of high amounts. The cells in the early lesions had an increased mitotic index, but cells from livers with early lesions did not have an increased survival in cell culture or the ability to grow in soft agar. The more developed lesions, hyperplastic nodules, also did not store iron, had persistent glycogen, did not display increased concanavalin A agglutinability, and were not independent secretors of high levels of alpha-fetoprotein. Similarly, nodule cells were proliferative but did not display an increase in survival in cell culture. In addition, both iso- and autotransplantation of nodules into mammary fat pads resulted in persistence but not growth of nodule cells. On the other hand, hepatocellular carcinomas regularly grew upon transplantation. Thus, early lesions and hyperplastic nodules were proliferative lesions did not possess autonomous growth capability comparable to that of hepatocellular carcinomas.

Topics: 2-Acetylaminofluorene; alpha-Fetoproteins; Animals; Cell Aggregation; Cell Transformation, Neoplastic; Cells, Cultured; Concanavalin A; Hyperplasia; Iron; Liver Glycogen; Liver Neoplasms; Neoplasms, Experimental; Precancerous Conditions; Rats

Investigations were performed in 6 cases of epidermodysplasia verruciformis and 2 healthy family members. Nonspecific cell-mediated immunity (CMI) was studied by measuring response to phytohemagglutinin (PHA) and concanavalin A (Con A), percentrages of E- and EAC-rosette-forming lymphocytes, bacterial skin tests, and allergic reactions to dinitrochloro-benzene (DNCB). Impairment of CMI was manifested by reduction in the percentage of E rosettes, and lowered response to PHA, and- to a lesser degree- to Con A. The immune response to DNCB sensitization was invariably negative. Impairment of CMI was greater in cases of long duration and with extensive lesions. The cases of similar duration and extent of lesions, which never showed tendency to tumor formation, were not different in CMI in comparison with cases with numerous tumors. Only in cases with very advanced tumors CMI was impaired parallel to the gravity of the patient's general condition.

Topics: Adolescent; Adult; Child; Concanavalin A; Dinitrochlorobenzene; Female; Humans; Immunity, Cellular; Lectins; Lymphocyte Activation; Lymphocytes; Male; Precancerous Conditions; Skin Diseases; Skin Tests; Syndrome

A previous study demonstrated that cells of transplantable hepatocellular carcinomas were agglutinated by the plant lectin concanavalin A, while normal hepatocytes were not. In the present experiments, 95% or more of cells obtained from primary hepatocellular carcinomas which resulted from exposure of rats to N-2-fluorenylacetamide were agglutinated by this lectin. Exposure to this carcinogen also produces grossly visible foci of morphologically and biochemically altered hepatocytes which have been termed hepatic (hyperplastic; premalignant, neoplastic) nodules. Although these hepatocyte aggregates are generally accepted as precursors of the hepatocellular carcinomas, no agglutination was detected when their cells were exposed to concanavalin A. These results indicate that concanavalin A agglutinability is not acquired as a result of tumor transplantation. Furthermore, they suggest that significant alterations must occur in the cells of hepatic nodules prior to the manifestation of malignant behavior.

Topics: 2-Acetylaminofluorene; Agglutination; Animals; Carcinoma, Hepatocellular; Concanavalin A; Liver Neoplasms; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred ACI

Fibroblasts underlying human uterine cervical dysplasia, carcinoma in situ, and invasive carcinoma are agglutinable by concanavalin A (Con A) but not by wheat germ agglutinin, except at very high concentration. Studies with low levels of Con A show that maximal agglutination is obtained with fibroblasts from invasive carcinoma, while the fibroblasts underlying dysplasia give minimal agglutination reactions. Fibroblasts underlying carcinoma in situ give agglutination reactions halfway between those obtained with fibroblasts underlying dysplasia and invasive carcinoma. An epithelial-like cell line obtained from a case of dysplasia shows agglutinability by Con A very similar to that obtained with fibroblasts underlying dysplasia. These epithelial-like cells are also not agglutinable by wheat germ agglutinin. Treatment of the cervical cells, both epithelial and fibroblasts, with neuraminidase leads to slight increase in agglutination by both Con A and wheat germ agglutinin. Marked increase in agglutination is not obtained even after treatment with high concentration of neuraminidase (10 units/10(6) cells). Marked agglutinability, however, is observed after trypsin treatment. The results suggest that, while the fibroblasts obtained from normal cervix are not agglutinable by Con A, surface alterations necessary for Con A-specific agglutination exist in fibroblasts during the early stage of development of uterine cervical epithelial neoplasia (dysplasia) and increase with the progression through carcinoma in situ to invasive carcinoma. Loss of cell surface sialic acids may result in a slight increase in agglutinability, but some other mechanism(s) is likely to be involved in alteration of surface properties that lead to marked agglutinability of the human uterine cervical cells obtained from cancer precursor lesions.

Topics: Agglutination; Carcinoma; Carcinoma in Situ; Cell Line; Cells, Cultured; Concanavalin A; Epithelial Cells; Epithelium; Female; Fibroblasts; Humans; Lectins; Neuraminidase; Precancerous Conditions; Uterine Cervical Neoplasms