Increased class 3 semaphorin expression modulates the invasive and adhesive properties of prostate cancer cells.
The class 3 semaphorins, sema3A and sema3C, provide important guidance cues in cell development and in cancer; however, the role of these semaphorins in prostate cancer is not known. We report here that sema3A transfected cells exhibit decreased invasion and adhesion in Matrigel-based assays and that sema3C transfected cells exhibit increased invasive and adhesive characteristics. Important adhesion proteins were differentially modulated in sema3A and sema3C cells in a manner consistent with their subsequent invasive and adhesive characteristics. E-cadherin expression as determined by Western blot analysis was strongly upregulated in sema3A transfected cells, but strongly downregulated in sema3C transfected cells compared to untransfected and mock empty vector-transfected PC-3 cells. beta-catenin levels were not changed in sema3A transfected cells; however, sema3C transfected cells had lower expression of this protein. Sema3C transfected cells exhibited greater cellular membrane expression of certain alpha integrins as compared to untransfected and sema3A transfected cells, a characteristic associated with increased adhesion and invasion. These data indicate that the invasive ability of sema3A and sema3C transfected PC-3 cells is, in part, correlated with adhesion protein expression and adhesive ability to constituents of neighboring cells and the extracellular matrix.
Herman
Jeffery G
JG
The Pharmacology and Toxicology Graduate Program, Department of Pharmaceutical Sciences, and the Cancer Prevention and Research Center, College of Pharmacy, Washington State University, Pullman, WA 99164-6713, USA.
Meadows
Gary G
GG
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000096:biosynthesis; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D040121:Semaphorin-3A / Q000096:biosynthesis* / Q000502:physiology; D039961:Semaphorins / Q000096:biosynthesis* / Q000502:physiology; D014162:Transfection; D051176:beta Catenin / Q000096:biosynthesis
D015820:Cadherins; D016023:Integrins; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D039961:Semaphorins; D051176:beta Catenin