Synthesis of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein by human breast epithelial cells.
Malignant and uninvolved human breast tissues were maintained in organ culture for 3 to 6 days. Under these conditions, the three-dimensional glandular architecture is maintained with the least disruption of tissue integrity. The biosynthesis and release of glycoproteins were studied by using the incorporation of [14C]glucosamine and [14C]leucine by the breast surgical specimens. Five major families of labeled glycoproteins were identified from culture supernatants using two-dimensional gel electrophoresis. Quantitative immunoprecipitation established that 16 to 30% of the total of labeled glycoproteins were recognized as normal serum components. Two of these glycoproteins were antigenically related to normal human serum components as demonstrated with crossed immunoelectrophoresis. Evidence was obtained for the active synthesis of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein by human breast epithelial cells. alpha 1-Antichymotrypsin accounted for 0.9 to 7.8% of the biosynthetically labeled glycoproteins from organ culture supernatants. This component was 11.9% of the glycoproteins released by a monolayer culture of the established breast carcinoma cell line, MCF-7. alpha 1-Acid glycoprotein made up 0.7 to 3.1% of the labeled glycoproteins. alpha 1-Antichymotrypsin is a known neutral serine proteinase inhibitor with a particularly strong affinity for cathepsin G. alpha 1-Acid glycoprotein may function primarily as a potent immunomodulator by suppressing lymphoblastogenesis. These glycoproteins may thus have regulatory roles in the proteolytic modification of breast tissue and represent the tissue's own protecting shield against invading leukocytes.
D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D008970:Molecular Weight; D009924:Organ Culture Techniques; D009961:Orosomucoid / Q000096:biosynthesis* / Q000302:isolation & purification; D000514:alpha 1-Antichymotrypsin
D009961:Orosomucoid; D000514:alpha 1-Antichymotrypsin; D002918:Chymotrypsin