Gerald B. Dermer

Origin of bronchioloalveolar carcinoma and peripheral bronchial adenocarcinoma

The morphologic distribution of newly synthesized glycoproteins in a bronchioloalveolar carcinoma and in a peripheral bronchial adenocarcinoma with areas of bronchioloalveolar differentiation was determined and compared with bronchiolar epithelium and type II alveolar cells. Tissues were maintained in vitro, and autoradiography was used to reveal locations of glycoproteins metabolically labelled with 3Hglucosamine. Both tumors displayed glycoprotein secretory activity as most incorporated radioactivity was rapidly released from cells. Silver grains were associated with cytoplasmic granules and mucinlike secretions in the bronchioloaveolar carcinoma and granules plus unidentified secretions in the bronchial adenocarcinoma. Clara cells exhibited an association of newly synthesized glycoproteins with cytoplasmic granules similar to those found in the tumors. In bronchiolar ciliated epithelium, as in bronchial ciliated cells and central bronchogenic adenocarcinomas, glycoproteins accumulated over apical cell surfaces and were not rapidly secreted. Type II cells incorporated label into secreted contents of cytosomal inclusions and unidentified cytoplasmic material. The observations suggest that a bronchioloalveolar carcinoma and a peripheral bronchogenic adenocarcinoma are distinct from common bronchogenic adenocarcinomas and are derived from secretory cells that resemble bronchiolar Clara cells.

Cell surface properties of ascites sublines of the 13762 rat mammary adenocarcinoma: Relationship of the major sialoglycoprotein to xenotransplantability

Abstract The relationship between cell surface sialoglycoprotein and xenotransplantation has been investigated in ascites sublines of the 13762 rat mammary adenocarcinoma. Two of the five sublines (MAT-C and MAT-C1) can be transplanted into mice. These two sublines also have the greatest amounts of total, trypsin-releasable and neuraminidase-releasable sialic acid. Chemical labeling using periodate treatment followed by [ 3 H]borohydride reduction indicates that most of the protein-bound sialic acid is associated with a single major sialoglycoprotein (or family of glycoproteins) with a low mobility on polyacrylamide gels in dodecyl sulfate (SDS). This glycoprotein, denoted ASGP-1, is also labeled by lactoperoxidase and 125 I, indicating its presence at the cell surface. Metabolic labeling with [ 3 H]glucosamine shows that ASGP-1 is the major glycosylated protein in both xenotransplantable (MAT-C1) and non-xenotransplantable (MAT-B1) sublines, representing >70% of the protein-bound label in each. The labeling studies indicate that the non-xenotransplantable subline does not have a substantially greater amount of ASGP-1 on its cell surface. Likewise cationized ferritin labeling and transmission electron microscopy (TEM) do not show substantially greater amounts of negatively charged groups distributed along the cell surfaces of MAT-C1 than of MAT-B1 cells. The results indicate that the transplantation differences between these sublines cannot be explained solely by the presence of a major sialoglycoprotein at the cell surface.

Autoradiography of cellular glycoproteins reveals histogenesis of bronchogenic adenocarcinomas.

Primary and metastatic human bronchogenic adenocarcinomas, excluding bronchioloalveolar and large cell types, and normal bronchi were studied to find out if the tumors displayed a common type of glyco‐protein metabolism that was also shared by one or more bronchial epithelial cell types. For comparison, the glycoprotein metabolism of a metastatic pancreatic adenocarcinoma was also investigated. Tissues were maintained in vitro, and the cellular distribution of glycoproteins, metabolically labelled with 3H‐glucosamine, was determined by light and electron microscopic autoradiography. Intense reactions in the form of silver grains over luminal surfaces of primary bronchogenic adenocarcinomas and those metastatic to pleural fluids indicated that the synthesis of cell coat (glycocalyx) glycoproteins predominated. In the pancreatic adenocarcinoma, the synthesis of secretory glycoproteins predominated, reflecting a histogenesis from secretory epithelium. In bronchi, only ciliated epithelium exhibited a distribution of newly synthesized glycoproteins similar to that observed in the bronchogenic adenocarcinomas. These observations suggest that bronchogenic adenocarcinomas share a common histogenesis and most likely arise from a cell type committed to differentiation into ciliated epithelium.