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.