An autocrine motility factor secreted by the Dunning R-3327 rat prostatic adenocarcinoma cell subtype AT2.1.
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 AT2.1 tumor cell subline AT2.1-AMF, prepared by concentration of components less than or equal to 30 kDa- in size and washed free of low-molecular-weight growth factors, stimulated motility of AT2.1 cells in modified Boyden chamber migration assays. This stimulated migration was dose-dependent, and by checkerboard analysis was both chemotactic and chemokinetic. AT2.1-AMF activity was labile to heat, acid, base, reduction, oxidation, and proteases. Lyophilization and treatment with 6M urea caused a mild decrease (less than 20%) 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. AT2.1 cell migration to AT2.1-AMF was inhibited by 2 hr pre-treatment with cholera toxin (0.1 microgram/ml) or forskolin (100 microM), but not altered by 2 hr pre-treatment with pertussis toxin (1.0 microgram/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.
Evans
C P
CP
Division of Surgery, Walter Reed Army Institute of Research, Washington, D.C.
Walsh
D S
DS
Kohn
E C
EC
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002630:Chemotactic Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D010450:Endopeptidases / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002630:Chemotactic Factors; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D010450:Endopeptidases