Tumor Cell Autocrine Motility Factor Is the Neuroleukin/Phosphohexose Isomerase Polypeptide1

To date, the structure of the autocrine motility factor (AMF), a tumorsecreted cytokine which stimulates cell migration in vitro and metastasis in rim, is unknown. Here, AMF secreted by Gc-4 PF murine fibrosarcoma into a protein-free conditioned media was isolated, purified, and microsequenced. The results demonstrate that AMF is the previously cloned cytokine and enzyme designated as neuroleukin, and phosphohexose isomerase (PHI), which has been independently implicated in cell motility, and to be a cancer progression marker. PHI catalyzes isomerization of glucose 6-phosphate to fructose 6-phosphate and is specific for both sugars. Murine AMF exhibits the enzymatic properties of PHI and rabbit heart PHI-stimulated mouse fibrosarcoma cells' motility similar to those of the endogenous AMF. Specific PHI inhibitors (carbohydrate phos phates) inhibited enzymatic activity and AMF-induced cell motility.