heparitin-sulfate and Uterine-Cervical-Neoplasms

Mucosal antibodies against human papillomavirus type 16 (HPV16) capsids have been detected in infected women. To determine whether these antibodies recognize and block the receptor site mediating attachment of HPV16 to heparan sulfate, mucus samples from 126 HPV16-associated low-grade squamous intraepithelial lesion (LSIL) and 85 cervical cancer patients, previously found to react to HPV16 virus-like particles (VLP), and 101 normal controls were tested in an inhibition assay, using HPV16 VLP and heparan sulfate proteoglycan-coated plates. Inhibition levels of 9.3-67.2% were mediated by type-specific antibodies in 94.4% of LSIL patients. Cervical cancer cases showed significantly lower levels of inhibition than LSIL samples (P < 0.0001). The potential of antibodies to inhibit infection was explored in a pseudoinfection system using HPV16 pseudovirions. Inhibition of pseudoinfection by LSIL samples was significantly higher than that observed in the controls (P < 0.001) and cervical cancer cases (P < 0.005). These results indicate that mucosal antibodies inhibiting binding of VLP to heparan sulfate are developed in most LSIL patients, but are hardly present in cervical cancer patients.

Topics: Animals; Antibodies, Viral; Female; Heparitin Sulfate; Human papillomavirus 16; Human papillomavirus 18; Humans; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Mice; Papillomavirus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears; Virion

Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans (HS-GAG) and most of its biological functions are considered to be associated with this process. The aims of this study are to investigate its expression in cervical neoplasms.. We investigated the expression of both the syndecan-1 core protein and cell-surface HS-GAG by immunohistochemistry in 53 cervical intraepithelial neoplasm (CIN), 19 microinvasive, 143 invasive cervical cancers, and 29 metastatic lymph node samples, and analyzed correlations with various clinicopathological features.. The progression of CIN to early invasive cancer was found to associate with reduced levels of both syndecan-1 and HS-GAG expression. In squamous cell carcinomas, HS-GAG expression was significantly lower in cases with lymph-vascular space invasion. Additionally, the overall survival rates for patients exhibiting low HS-GAG expression was significantly lower than patients exhibiting high HS-GAG expression (P = 0.019). Low HS-GAG expression in positive nodes was determined to be a disease-free and overall survival prognostic factor (P = 0.028 and P = 0.018, respectively).. The loss of syndecan-1 and HS-GAG expression is an early event in cervical carcinogenesis. The loss of HS-GAG expression particularly in positive nodes can serve as an indicator of aggressive disease potential and poor prognosis in patients with invasive cervical cancer.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Heparitin Sulfate; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; Membrane Glycoproteins; Middle Aged; Neoplasm Invasiveness; Prognosis; Proteoglycans; Syndecan-1; Syndecans; Treatment Outcome; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The important components of mucopolysaccharides and collagen have been analyzed in tissues of control and carcinoma of uterine cervix. Among these components hyaluronic acid and chondroitin sulphate levels were found to be increased, whereas decreased level of collagen was observed in uterine cervical carcinoma. Serum cathepsin B, D and acid and alkaline phosphatases have also been analyzed in controls and carcinoma patients before and after treatments. The activities of these enzymes have been found to increase prominently in advanced stages. Among these enzymes cathepsin B and alkaline phosphatase have exhibited remarkable increase in activity in uterine cervical carcinoma. Different modes of treatment exerted reversion of the elevated activities of these enzymes. However, combined therapy type II (radiation combined with cisplatin and cyclophosphomide) seems to be more effective in reverting the activities of these enzymes to normal levels.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Cathepsins; Chondroitin Sulfates; Collagen; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Middle Aged; Pepsin A; Peptide Hydrolases; Uterine Cervical Neoplasms

An immunohistochemical study of samples from 12 cervical carcinomas was carried out using monoclonal antibodies against laminin (L) and heparan sulfate proteoglycan (HSP). Cryostat sections of operative and biopsy specimens were processed by the immunoperoxidase method. L and HSP were identified in the basal membrane of normal and neoplastic epithelium. Basal membrane disruptions were found in in situ, microinvasive and invasive carcinomas. However, in the first group they were less common and occurred only in the presence of lymphohistiocytic infiltration of the underlying stroma. An inverse relationship was established between depth of invasion and amount of L and HSP in the basal membrane of tumor epithelium.

Topics: Adult; Carcinoma, Squamous Cell; Female; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Immunoenzyme Techniques; Laminin; Middle Aged; Neoplasm Invasiveness; Proteoglycans; Uterine Cervical Neoplasms