Elevation of seprase expression and promotion of an invasive phenotype by collagenous matrices in ovarian tumor cells.
Tumor cells do not constitutively exhibit invasive activity, but rather, can be transiently induced to adhere and form lesions. We report here that the expression of seprase, a dominant EDTA-resistant gelatinase in malignant tumors, is dependent on tumor cell exposure to type I collagen gel (TICg). The induced seprase expression of ovarian tumor cells influences their collagen contraction and invasion capability. Importantly, tumor cells with reduced seprase expression, due to manipulation by RNA interference, showed a reduction of TICg contraction in the gel contractility assay, inhibition of tumor cell invasion through TICg as shown by a transwell migration assay and inhibition of peritoneal membrane tumor lesion in a mouse model. In addition, mAb C27, an antibody against beta1 integrin, which blocks cellular avidity to TICg, can induce seprase RNA expression and promote the invasive phenotype and metastatic potential of ovarian tumor cells. Thus, collagenous matrices in the tumor cell niche induce the expression of seprase and initiate tumor invasion and metastatic cascades.
Kennedy
Alanna
A
Department of Medicine, State University of New York, Stony Brook, NY 11794-8154, USA.
Dong
Huan
H
Chen
Donghai
D
Chen
Wen-Tien
WT
D000818:Animals; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D000099167:Fibroblast Activation Protein Alpha
D003094:Collagen; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C478147:seprase, human