title: Promising noninvasive cellular phenotype in prostate cancer cells knockdown of matrix metalloproteinase 9.
abstract: Cell surface interaction of CD44 and MMP9 increases migration and invasion of PC3 cells. We show here that stable knockdown of MMP9 in PC3 cells switches CD44 isoform expression from CD44s to CD44v6 which is more glycosylated. These cells showed highly adhesive morphology with extensive cell spreading which is due to the formation of focal adhesions and well organized actin-stress fibers. MMP9 knockdown blocks invadopodia formation and matrix degradation activity as well. However, CD44 knockdown PC3 cells failed to develop focal adhesions and stress fibers; hence these cells make unstable adhesions. A part of the reason for these changes could be caused by silencing of CD44v6 as well. Immunostaining of prostate tissue microarray sections illustrated significantly lower levels of CD44v6 in adenocarcinoma than normal tissue. Our results suggest that interaction between CD44 and MMP9 is a potential mechanism of invadopodia formation. CD44v6 expression may be essential for the protection of non-invasive cellular phenotype. CD44v6 decrease may be a potential marker for prognosis and therapeutics.
authors.affiliation: Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Gupta
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sadashivaiah
authors.forename: Wantao
authors.initials: W
authors.lastname: Chen
authors.forename: Abraham
authors.initials: A
authors.lastname: Schneider
authors.forename: Meenakshi A
authors.initials: MA
authors.lastname: Chellaiah
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; C112697:CD44v6 antigen; D018960:Hyaluronan Receptors; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9