Modulation of the growth of human and murine cell lines in vitro by recombinant human tumor necrosis factor-α (rTNF-α) and recombinant human interferon-γ (rIFN-γ) was investigated. rTNF-α had cytostatic or cytolytic effects on only some tumor cell lines. When administered together with rIFN-γ, rTNF-α showed enhanced antiproliferative effects on a subset of the cell lines tested. In contrast to its effects on sensitive tumor cells, rTNF-α augmented the growth of normal diploid fibroblasts. Variations in the proliferative response induced by rTNF-α were apparently not due to differences in either the number of binding sites per cell or their affinity for rTNF-α. These observations indicate that the effects of rTNF-α on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo.

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The immunochemical and structural characteristics of the alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] from mouse teratoma stem cells derived from the teratoma (ascitic and solid tumors and the F9 and PCC4 cell lines) have been compared to those of the alkaline phosphatases expressed in normal mouse placenta and several adult organs. Crossreactivity of the stem celalkaline phosphatase with antisera reacting with placental, kidney, liver, and brain alkaline phosphatases indicated that the stem cell enzyme had common antigenic determinants. Structural studies utilizing two-dimensional electrophoresis of the 32P-labeled alkaline phosphatase subunits showed that the stem cell, placental, and kidney alkaline phosphatases differed only in their sialic acid content and comigrated after removal of terminal sialic acid by neuraminidase digestion. Furthermore, one-dimensional peptide mapping of partial proteolysis fragments from 32P-labeled enzymes demonstrated identical fragmentation patterns for the stem cell and somatic enzymes. These immunochemical and structural data indicate that the stem cell alkaline phosphatase is the same core enzyme as that produced in the mouse placenta and kidney, with different amounts of terminal sialic acid. The one mouse alkaline phosphatase examined that differed from the other enzymes was the intestinal alkaline phosphatase. This isoenz me was not immunochemically crossreactive with the other arkaline phosphatases, did not comigrate in two-dimensional electrophoresis after neuraminidase digestion, and did not give identical peptide maps after partial proteolysis. Alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] has been the subject of a number of studies as a biochemical marker for the totipotential stem cells of the mouse teratoma. Damjanov et al.(1) first cited the enzyme as a histochemical marker for these cells. Bernstine et al. (2) showed that the proportion of stem cells in cell lines derived from the mouse teratoma cell line OTT-6050 could be correlated with alkaline phosphatase specific activity. The use of the stem cell alkaline phosphatase as a specific marker for the totipotential state of the stem cell would be dependent on the uniqueness of this gene product to the stem cell population. Based on the behavior of the enzymes in thermal inactivation and D-phenylalanine inhibition studies by Bernstine et al. (2), the stem cell enzyme was found to resemble the isoenzymes of mouse kidney and placenta but differed from the isoenzymes of mouse liver and intestine. Because functional studies on crude cell extracts are not adequate as a sole criterion for determining differences between gene products, Wada et al. (3) compared the enzymes of the ascitic and solid tumor forms of OTT-6050 with those of mouse kidney and placenta by using sodium dodecyl sulfate (NaDodSO4)/polyacrylamide gel electrophoresis and found that solid tumor and ascitic tumor enzymes had a subunit molecular...

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