Plasma membrane retrieval in neoplastic pancreatic acinar cells.

Abstract

The dynamics of plasma membrane retrieval has been studied in the pancreatic acinar carcinoma in order to determine if neoplastic cells exhibiting a heterogeneity of cytodifferentiation states retain the capacity to interiorize and recycle plasma membrane. To this end, the plasma membranes of neoplastic pancreatic acinar cells were labeled with radioiodinated cationic ferritin (125I-CF), and the fate of the tracer was monitored by quantitative electron microscopic autoradiography. The undifferentiated granule-deficient cells of the tumor internalized membrane-bound 'RI-CF and sequestered it predominantly in lysosomes. By contrast, the differentiated granule-rich cells internalized significantly more membrane-bound 1"I-CF,.and the tracer was localized in secretory granules and in lysosomes. The data suggest that neoplastic cells retain the capability of retrieving plasma membrane and that the dynamics of the process is correlated with the state of cytodifferentiation of the neoplastic cells.Cationic ferritin (CF) has recently been used to study the retrieval of plasma membrane in the dissociated cells of the anterior pituitary gland (1) and the thyroid follicular cells (2). The significant finding from these studies is that although some of the retrieved membrane-is sequestered in lysosomes and presumably degraded, the remainder reaches organelles that comprise the secretory pathway [the Golgi cisternae, secretory granules, and elements of GERL (Golgi-associated endoplasmic reticulum from which lysosomes form) (3)] to be recycled in successive waves of the secretory cycle. The existence of considerable. membrane traffic between plasma membrane and the Golgi cisternae and lysosomes in both normal plasma cells and myeloma cells has been demonstrated by Ottosen et al. (4). However, plasma-membrane recycling has not been well-documented for neoplastic epithelial cells. As a result, in the present investigation a transplantable rat pancreatic acinar carcinoma (5) was used as a model system to determine whether or not carcinoma cells retain the capability of retrieving plasma membrane. Because the cells that comprise this tumor exhibit well-characterized cytodifferentiated states (6, 7), an additional aim was to ascertain whether undifferentiated neoplastic pancreatic acinar cells with a paucity of secretory (zymogen) granules internalize plasma membrane and distribute it in a manner different from that of the differentiated, well-granulated cell types. To accomplish this, the plasma membrane of pancreatic acinar carcinoma cells, maintained in short-term culture, was labeled with radioiodinated CF (125I-CF), and the fate of the plasma membrane in secretory granule-deficient (undifferentiated; GD) and secretory granule-rich (differentiated; GR) neoplastic cells was monitored by quantitative electron microscopic autoradiography.MATERIALS AND METHODS Materials. Materials used were purchased as follows: horse spleen ferritin (cadmium free), twice crystallized from Calbiochem-Behring; Na'"I from Amersham; a-chymot...

Role of the golgi apparatus in cellular pathology

“…Aspects of endocytic membrane trafficking in tumor cells have been less well studied. Pancreatic acinar carcinoma cells, when supplied with radiolabeled cationic ferritin, retained the capacity to interiorize and recycle plasma membranes (Kanwar et al, 1983). As determined by electron microscopic autoradiography, the tracer internalized in undifferentiated granule-deficient cells primarily to lysosomes.…”