Glycoprotein synthesis as a function of epithelial cell arrangement: biosynthesis and release of glycoproteins by human breast and prostate cells in organ culture.
We demonstrate that a technique is available to investigate glycoprotein synthesis in organ cultures of human breast and prostate surgical specimens where the 3-dimensional epithelial cell arrangement remains intact. Malignant breast and prostate epithelium maintained their capacity to synthesize glycoproteins for at least 3 days as followed by the incorporation of [3H]glucosamine into macromolecules. Over 70% of incorporation was by malignant cells as judged by autoradiography. Labeled glycoproteins were released into glandular lumina and consequently into the culture fluid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed predominantly one group of macrmolecules released with an apparent molecular weight of 48,000 +/- 6,000 daltons. This glycoprotein was found in all of the breast specimens studied, which included 1 medullary, 1 infiltrating lobular, and 8 infiltrating duct carcinomas. The pattern was independent of the availability of estrogen receptors. A similar glycoprotein was also observed in the culture media from a Grade I and a Grade II well-differentiated infiltrating prostate carcinoma. Incorporation was below the level of detection in 4 of 6 cases of benign prostatic hyperplasia. A more complex pattern of labeled glycoproteins was found in the media of a Grade II and a Grade III poorly-differentiated prostate carcinoma. The established human mammary carcinoma cell line MCF-7 synthesized and released a similar 48,000 molecular weight glycoprotein but additional components with larger molecular weights were also released. An intriguing interpretation that 3-dimensional tissue integrity restricts some glycoprotein synthesis is discussed. Cells grown in 2-dimensional monolayers could escape from such a topographic restriction and express additional families of glycoproteins.
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004848:Epithelium / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D006023:Glycoproteins