Anomalous structure of urinary chondroitin sulfate from cancer patients. A potential new marker for diagnosis of neoplasias.
BACKGROUND
Chondroitin sulfate is significantly increased in tumors (10 to 100 times) when compared to the amounts present in normal adjacent tissues. To investigate if the changes in concentration of chondroitin sulfate could be reflected in the urine of cancer patients we have analyzed the chondroitin sulfate excreted by 44 patients with different types of tumors, 50 normal individuals and 15 patients with unrelated diseases.


METHODS
The identification and structural analyses of the sulfated glycosaminoglycans were made by electrophoresis and degradation with specific enzymes (chondroitinases AC and ABC), identification/quantitation of their disaccharide products by chromatography (paper and HPLC) and chemical determinations.


RESULTS
The disaccharide products formed from chondroitin sulfate of the 44 cancer patients by action of chondroitinase ABC show a substantial relative increase of non sulfated disaccharide (32.1% +/- 15.2) with a relative decrease of 6-sulfated disaccharide (28.9% +/- 11.5) and 4-sulfated disaccharide (39.0% +/- 13.5) when compared to the chondroitin sulfate of normal subjects (9.1% +/- 2.2, 40.6% +/- 4.5 and 50.2% +/- 4.5, respectively) or from patients with unrelated diseases. There is a direct correlation between the non sulfated disaccharide content and the stage of malignancy of the cancer patients. A significant change of the ratio of chondroitin sulfate and heparan sulfate and a decrease in the electrophoretic migration of chondroitin sulfate were also observed in cancer patients.


CONCLUSIONS
All the cancer patients analyzed so far have shown the structural anomaly of the urinary chondroitin sulfate and this may be useful in the diagnosis and follow up of cancer therapy.
Dietrich
C P
CP
Departamento de Bioquimica, Escola Paulista de Medicina, São Paulo, Brazil.
Martins
J R
JR
Sampaio
L O
LO
Nader
H B
HB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000737:chemistry / Q000652:urine; D004587:Electrophoresis, Agar Gel; D006025:Glycosaminoglycans / Q000652:urine; D006497:Heparan Sulfate / Q000652:urine; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000601:surgery / Q000652:urine*; D011184:Postoperative Period; D012016:Reference Values
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002809:Chondroitin Sulfates; D004187:Disaccharides; D006025:Glycosaminoglycans; D006497:Heparan Sulfate