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Updated: Aug 9, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Production of a serine-protease with macrophage migration-inhibitory factor activity by virus-transformed cells and
Abstract:
BALB/c mouse 3T3 cells transformed by simian virus 40 (SV3T3), baby hamster kidney cells transformed by polyoma virus or Rous sarcoma virus, and a range of neoplastic human cell lines release material that inhibits the migration of macrophages and lymphocytes. Similar migration-inhibitory factor (MIF) activity was not detected in supernatants from cultures of untransformed 3T3 or baby hamster kidney cells and a variety of human diploid cell strains. Physico-chemical characterization of the MIF produced by SV3T3 and HeLa cells revealed substantial similarities with the MIF produced by mitogen-activated human peripheral lymphocytes. MIF released by tumor cells is inhibited by pancreatic and soybean trypsin inhibitors and by diisopropylfluorophosphate, indicating that it is a serine-protease. Comparison of MIF produced by SV3T3 cells with a serine-protease plasminogen activator released by the same cells indicated that the latter is more heat labile and has a more heterogenous elution profile after chromatography on Sephadex G-75. The possible role of MIF in causing proteolytic modification of the surface properties of tumor cells and in altering cell-mediated immune responses to neoplastic cells is discussed.
Insights
Tumor cells release migration-inhibitory factor (MIF) that affects immune cells. This serine-protease is similar to that produced by lymphocytes, suggesting a role in immune response modulation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Neoplastic cells, including SV40-transformed mouse 3T3 cells, polyoma virus- or Rous sarcoma virus-transformed baby hamster kidney cells, and various human tumor cell lines, secrete a factor that inhibits immune cell migration.
- This migration-inhibitory factor (MIF) activity was absent in cultures of normal, untransformed cells.
Purpose of the Study:
- To characterize the migration-inhibitory factor (MIF) produced by tumor cells.
- To compare tumor cell-derived MIF with lymphocyte-derived MIF.
- To investigate the enzymatic nature and potential role of tumor cell-derived MIF in cancer immunology.
Main Methods:
- Cell culture of various transformed and non-transformed cell lines (SV3T3, baby hamster kidney cells, human tumor lines, human diploid strains).
- Collection and analysis of cell culture supernatants for migration-inhibitory activity.
- Physicochemical characterization of MIF, including protease inhibition assays (trypsin inhibitors, diisopropylfluorophosphate) and chromatographic analysis (Sephadex G-75).
- Comparison with plasminogen activator activity in SV3T3 cells.
Main Results:
- Tumor cell lines release a potent migration-inhibitory factor (MIF) for macrophages and lymphocytes.
- The MIF from SV3T3 and HeLa cells shares physicochemical properties with MIF from activated human lymphocytes.
- Tumor cell MIF is sensitive to serine protease inhibitors, identifying it as a serine-protease.
- Tumor cell MIF differs from plasminogen activator in heat lability and chromatographic behavior.
Conclusions:
- Tumor cells secrete a serine-protease MIF that is biochemically similar to the lymphocyte-derived counterpart.
- This tumor-derived MIF may play a role in altering the tumor microenvironment and modulating cell-mediated immune responses.
- Further research is warranted to explore the implications of tumor cell MIF in cancer progression and immune evasion.
