Modulation of cell proliferation by human recombinant interleukin-1 and immune interferon.

The growth-modulating effects of recombinant alpha- and beta-forms of human interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) were examined with several human cell lines. Exposure to combinations of IL-1 and IFN-gamma resulted in three categories of cell response. The first was cell lines in which IL-1 stimulated growth and offset the growth inhibitory effects of IFN-gamma. These lines included the lung carcinoma CALU-1 and the colon carcinoma SW-48. The second was some of the cell lines that were refractory to IL-1 and that were inhibited by IFN-gamma alone. These included the cervical carcinoma HeLa, the transformed milk line HBL-100, and the myelogenous leukemia K562. The third group consisted of cells in which growth inhibition by IL-1 and IFN-gamma was additive. These included the mammary carcinomas MCF-7 and MDA-MB-415. The exception to this latter group was ME-180 in which significant additive inhibitory effects could not be demonstrated. IL-1 alone primarily induced a cytostatic effect in growth-inhibited cell lines. The cytolytic effect induced by IFN-gamma was increased in the presence of IL-1. The data support the conclusion that the effects on growth of IL-1 and IFN-gamma are mediated by different mechanisms.

Regulation of human amnion cell growth and morphology by sera, plasma, and growth factors.

The requirements of human epithelial cells derived from the amnion membrane for serum factors were investigated. The growth promoting effects of human whole blood serum (WBS), platelet-poor defibrinogenated plasma, and plasma-derived serum (PDS) were examined in primary cultures of these ectodermal cells. The numbers of population doublings recorded after 10 days in the presence of 10% WBS, defibrinogenated plasma, or PDS were 2.3, 2.0 or 1.5, respectively. Although dialysis of sera or plasma had little effect on growth promotion, it markedly decreased the capacity of plasma to maintain cells in culture beyond 10 days. The differences in growth activities could not be attributed to the presence of anticoagulant in plasma and PDS or to the presence of excess calcium in PDS. Platelet lysates and purified platelet-derived growth factor had no effect on growth. Amnion cell growth was enhanced by epidermal growth factor (EGF) or hydrocortisone, but the glucocorticoid did not condition cells to respond to growth factors. Insulin and fibroblast growth factor singly or in combination had no effect on cell replication. Giant cell formation accompanied maintenance in hydrocortisone with defibrinogenated plasma and PDS. Discrete regions of dense population appeared in the presence of hydrocortisone, EGF, and undialyzed supplements.

Inhibition of growth of human breast cancer cell line MCF-7 by serum derived from calcium chloride-clotted plasma.

The growth of MCF-7 cells, established from a metastatic mammary carcinoma, and of HBL-100 cells, derived from a primary culture of human milk, was examined in medium supplemented with whole blood serum (WBS), defibrinogenated plasma, and plasma-derived serum (PDS). PDS obtained from platelet-poor plasma collected with the anticoagulant citrate phosphate dextrose and clotted by the addition of calcium chloride did not promote the growth of MCF-7 cells as well as did WBS or platelet-poor defibrinogenated plasma alone. Growth-inhibitory activity was observed when final cell densities in the presence of PDS combined with fetal bovine serum (FBS) were compared with those in control cultures maintained in FBS alone. The level of this activity in PDS varied among donors. Inhibition was not observed with HBL-100 cells. Calcium chloride did not induce inhibitory activity when added to WBS or defibrinogenated plasma, and platelet components did not alter the level of inhibition in PDS. However, platelet extracts did affect the expression of inhibition when added to plasma before clotting. Activity was diminished following dialysis of PDS, which suggested that inhibition stemmed from a small-molecular-weight factor for which expression depended on the mechanism of plasma coagulation.

Origin, concentration and structural features of human mammary gland cells cultured from breast secretions.

This study traced the origin of cells observed in human breast secretion samples obtained during lactation and describes the appearance of these cells following prolonged maintenance in vitro. Human milk contains a large number of single vacuolated foam celsl and a small proportion of non-vacuolated epithelial cells in clusters. Foam cells are identified by their large size, the polarity of their cytoplasmic organelles, the variation in number and size of lipid vacuoles and the condensed chromatin of their eccentrically located nucleus. Both cell types originate by exfoliation from the mammary gland. This was established by comparing the structural characteristics of cells isolated from milk with those of the cuboidal cell linings of ducts and alveoli in lactating mammary tissue. Relatively pure populations of foam cells could be established from early lactation samples (3-7 days post/partum) while non-vacuolated epithelial cell clusters were more frequently cultured from late lactation specimens (1-10 days postweaning). Foam cells did not divide and lost cytoplasmic organization during prolonged culture. In contrast, non-vacuolated epithelium in clusters proliferated to form colonies of polygonal cells. These results, which imply that foam cells are an active form of the non-vacuolated mammary cells in clusters, call attention to one system for the study of the complex hormonal interactions necessary to induce and maintain lactation.