The minimum element of a synthetic peptide required to block prostate tumor cell migration.
Human prostate tumor cell invasion and metastasis are dependent in part on cell adhesion to extracellular matrix proteins and cell migration. We previously identified a synthetic D-amino acid tumor cell adhesion peptide called HYD1 (kikmviswkg) that supported adhesion of tumor cells derived from breast, prostate, ovary and pancreas tissue. Alanine substitution analysis and a peptide deletion strategy were used to determine the minimal element of HYD1 necessary for bioactivity in a prostate cancer cell line called PC3N. Bioactivity was measured by assays of cell adhesion, migration and ERK signaling. The most potent element of HYD1 necessary to support cell adhesion was kmvixw, the block to migration required xkmviswxx and activation of ERK signaling required ikmviswxx. The shortest sequence active in all three assays was iswkg. The HYD1 peptide contains overlapping elements required for adhesion, blocking migration and the activation of ERK signaling. These linear peptide sequences provide the starting point for development of novel compounds to target cancer cell adhesion and migration.
Sroka
Thomas C
TC
The Arizona Cancer Center, Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724, USA.
Marik
Jan
J
Pennington
Michael E
ME
Lam
Kit S
KS
Cress
Anne E
AE
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D048049:Extracellular Signal-Regulated MAP Kinases