Cohen M C, Cohen S
Hum Pathol. 1986 Mar;17(3):264-70. doi: 10.1016/s0046-8177(83)80219-6.
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.
在这篇简短的综述中，我们重点关注了一些研究，这些研究证明了存在能够改变多种肿瘤细胞功能的低分子量淋巴因子。我们发现，人源或鼠源的淋巴因子制剂含有一种蛋白质，即肿瘤迁移抑制因子（TMIF），它能够可逆地抑制多种肿瘤细胞的迁移。连续传代的动物肿瘤和人类自发性肿瘤对TMIF均有反应。对包括分子量、酶失活、单糖抑制谱以及杂交瘤的非协同产生等理化特性的测定，得出结论：TMIF不同于抑制非肿瘤细胞迁移的淋巴因子。TMIF可在体内被检测到，并且能够在体内改变肿瘤细胞的行为。此外，含TMIF的制剂能够抑制肿瘤细胞与内皮细胞单层的结合。尽管TMIF介导的迁移抑制与细胞毒性无关，但部分纯化的TMIF制剂对肿瘤细胞具有细胞生长抑制作用。细胞生长抑制并非迁移试验中观察到的结果的原因，因此这些特性在功能上是不同的。这三种活性出现在较窄的分子量范围内，不同于其他已知的淋巴因子，这表明存在一类独特的淋巴因子介质，它们具有影响肿瘤细胞功能特性的共同功能。我们建议将这些介质暂定为新调节素。对这一组淋巴细胞衍生的效应大分子的进一步表征将需要深入探究它们对列为肿瘤细胞“工作描述”的各种功能的影响，证明它们在体内的功效，并将各种因子纯化至同质。新调节素可能具有治疗潜力，因为它们调节的肿瘤细胞功能是那些与恶性潜能表达相关的功能。此外，正在进行研究以确定肿瘤细胞对这些因子的体外反应性是否与其体内生物学行为相关。最后，在肿瘤患者的血清或尿液中检测TMIF或相关淋巴因子可能有助于癌症的检测和/或隐匿性肿瘤转移及肿瘤复发的监测。
