An autocrine motility factor secreted by the dunning R-3327 rat prostatic adenocarcinoma cell subtype AT2.1
✍ Scribed by Christopher P. Evans; Douglas S. Walsh; Elise C. Kohn
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 566 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Tumor cell locomotion is an integral part of the metastatic process. We present a new autocrine motility factor (AMF) derived from the serum-free conditioned medium of the Dunning R-3327 rat prostate adenocarcinoma AT2. I tumor cell subline AT2. I-AMF, prepared by concentration of components c30 kDa in size and washed free of low-molecular-weight growth factors, stimulated motility of AT?. I cells in modified Boyden chamber migration assays. This stimulated migration was dose-dependent, and by checkerboard analysis was both chernotactic and chemokinetic. AT2. I-AMF activity was labile to heat, acid, base, reduction, oxidation, and proteases. Lyophilization and treatment with 6M urea caused a mild decrease (<ZOO/,) in migration-stimulating capability. Tumor-cell specificity was demonstrated for AMF of AT2.1 and AT3.1 Dunning sublines, and the A2058 human melanoma cell lines. AT2. I cell migration to AT2. I -AMF was inhibited by 2 hr pre-treatment with cholera toxin (0.1 pg/ml) or forskolin (100 p ~) , but not altered by 2 hr pre-treatment with pertussis toxin (1.0 pg/ml). This indicates that guanine nucleotide binding protein-mediated regulation of CAMP is involved in modulating the AT2.1 cell response to its AMF. The AT2.1-AMF belongs to a related family of tumor autocrine motility factors and represents a new model for understanding the role of tumor-cell migration in the metastatic process of human prostate cancer.