ABSTRACT
Expression of Fas (CD95, APO-1), a cell surface receptor capable of inducing ligand-mediated apoptosis, is involved in tissue homeostasis and elimination of targeted cells by natural killer and T cells. Corruption of this pathway, such as reduced Fas expression, can allow tumor cells to escape elimination and promote metastatic potential. In this study, the status of Fas expression has been examined in the parental SAOS human osteosarcoma cells that do not metastasize and in selected variants that cause lung metastases in 16 weeks (LM2) or 8 weeks (LM6) after i.v. injection into nude mice. Fas expression correlated with the metastatic potentials of the three cell lines. Northern and fluorescence-activated cell-sorting analyses indicated that LM6 cells expressed Fas at a lower level than seen in the parental cells. Infection of the LM6 cells with an adenoviral vector containing the murine interleukin (IL)-12 gene (AD:mIL-12) or treatment with recombinant murine IL-12 resulted in a dose-dependent up-regulation of FAS: The up-regulation of Fas by IL-12 was also demonstrated in human etoposide-resistant MDA-MB-231 breast cancer cells. [(3)H]Thymidine growth inhibition studies indicated that the cell surface Fas induced after IL-12 exposure was functional and able to mediate cell death on cross-linking with anti-FAS: We also demonstrate that this effect is independent of IFN-gamma. Whereas these cell lines are sensitive to IFN-gamma, incubation with IFN-gamma does not increase susceptibility to Fas-mediated cell death, nor do these cells produce IFN-gamma with or without IL-12 treatment. We hypothesize that expression of Fas may play a role in the elimination of metastatic tumor cells in the lung, an organ in which Fas ligand is expressed. The antitumor activity of IL-12 may be secondary in part to its ability to up-regulate Fas expression on tumor cells, which subsequently increases immune-mediated destruction of osteosarcoma cells.
Subject(s)
Bone Neoplasms/immunology , Breast Neoplasms/immunology , Interleukin-12/genetics , Interleukin-12/pharmacology , Osteosarcoma/immunology , fas Receptor/biosynthesis , Animals , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/physiology , Gene Transfer Techniques , Humans , Interferon-gamma/physiology , Mice , Osteosarcoma/genetics , Osteosarcoma/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Recombinant Proteins/pharmacology , Tumor Cells, Cultured , Up-Regulation/drug effects , Up-Regulation/physiology , fas Receptor/genetics , fas Receptor/physiologyABSTRACT
The breastfeeding experience of a mother and her preterm conjoined twins is described. Assisting the mother in achieving her breastfeeding goal presented unusual nursing-care problems in securing, positioning, and comforting the twins. This case report emphasizes the individualized support provided to this mother and her infants, which was a critical factor in their breastfeeding success.
