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Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide
H Watanabe1, K Takehana, M Date
1Department of Orthopedic Surgery, Gunma University School of Medicine, Japan.
Abstract:
To date, the structure of the autocrine motility factor (AMF), a tumor-secreted cytokine which stimulates cell migration in vitro and metastasis in vivo, 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 phosphates) inhibited enzymatic activity and AMF-induced cell motility.
Insights
Autocrine motility factor (AMF), a tumor cytokine, was identified as neuroleukin and phosphohexose isomerase (PHI). This enzyme
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The structure of autocrine motility factor (AMF), a tumor-secreted cytokine, was previously unknown.
- AMF stimulates tumor cell migration and metastasis.
- Identifying AMF's structure is crucial for understanding cancer progression.
Purpose of the Study:
- To isolate, purify, and microsequence AMF.
- To determine the identity and function of AMF.
- To investigate AMF's role in cancer cell motility.
Main Methods:
- AMF was isolated and purified from Gc-4 PF murine fibrosarcoma conditioned media.
- Microsequencing was used to determine AMF's amino acid sequence.
- Enzymatic assays and cell motility studies were performed.
Main Results:
- AMF was identified as neuroleukin, also known as phosphohexose isomerase (PHI).
- Murine AMF demonstrated PHI enzymatic activity.
- PHI inhibitors blocked both enzymatic activity and AMF-induced cell motility.
Conclusions:
- AMF is phosphohexose isomerase (PHI), an enzyme implicated in cell motility and cancer progression.
- PHI plays a direct role in mediating tumor cell migration.
- Targeting PHI may offer a strategy to inhibit cancer metastasis.