The role of lymphokines in neoplastic disease.
In this brief review, we have focused on studies demonstrating the existence of low-molecular-weight lymphokines that modify a number of tumor cell functions. We have found that lymphokine preparations of human or murine origin contain a protein, TMIF, that can reversibly inhibit the migration of a variety of tumor cells. Both serially passaged animal tumors and spontaneous human neoplasms respond to TMIF. Determination of physicochemical characteristics, including molecular weight, enzyme inactivation, monosaccharide inhibition profile, and noncoordinate production by hybridomas, has led to the conclusion that TMIF is distinct from the lymphokines that inhibit the migration of nonneoplastic cells. TMIF can be detected in vivo and can modify the behavior of tumor cells in vivo. In addition, TMIF-containing preparations can inhibit the binding of tumor cells to endothelial monolayers. Although migration inhibition by TMIF is not associated with cytotoxicity, partially purified TMIF preparations are cytostatic for tumor cells. Cytostasis is not the cause of the observed results in the migration assay, and these properties are therefore functionally distinct. These three activities, appearing within a narrow range of molecular weights, different from those of other known lymphokines, suggest the existence of a distinct class of lymphokine mediators with the common function of influencing functional properties of tumor cells. We propose that these mediators be tentatively defined as neomodulins. Further characterization of this set of lymphocyte-derived effector macromolecules will require thorough exploration of their effects on the various functions listed as tumor cell "job descriptions," demonstration of their in vivo efficacy, and purification of the various factors to homogeneity. The neomodulins are likely to have therapeutic potential, since the tumor cell functions that they regulate are those involved in the expression of malignant potential. In addition, studies are under way to determine whether the in vitro responsiveness of tumor cells to these factors might correlate with their in vivo biologic behavior. Finally, detection of TMIF or related lymphokines in serum or urine from patients with neoplasms could be useful in the detection of cancer and/or monitoring of occult tumor metastases and tumor recurrence.
M C
MC
Cohen
S
S
Cohen
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D004727:Endothelium / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007372:Interferons / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008222:Lymphokines / Q000032:analysis / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology; D016215:Macrophage-Activating Factors; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology
D007376:Interleukin-2; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D016215:Macrophage-Activating Factors; C043874:tumor migration inhibition factor; D007372:Interferons