The relationship of the virtual orbitals of self-consistent-field theory to temporary negative ions in electron scattering from molecules" (1990). Gordon Gallup Publications. 5.

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 b1 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. ' 2008 Wiley-Liss, Inc.Key words: seprase; FAP-a; gelatinase; collagen; ovarian tumor Epithelial ovarian cancer progresses by increased tumor cell proliferation and proteolytic activity that degrades the extracellular matrix (ECM) of the peritoneum. 1,2 Although blocking tumor progression by inhibiting protease activity is well-known, it is also possible that tumor progression could be suppressed by hindering the initial induction of these proteases.Type I collagen (TIC) is comprised of 3 strands of gelatin each of which contain adjoining glycine and proline residues. 3 It is this bond that is the known substrate for seprase. 4 Seprase was first described in the LOX human malignant melanoma cell line and is a type II transmembrane, 760 aa glycoprotein whose 97 kDa monomer homodimerizes to form a catalytically active complex of 170 kDa. 5-7 Molecular cloning of seprase revealed it to be identical to that of fibroblast activation protein a (FAP-a) in gene sequence, protein form, as well as dipeptidyl peptidase and gelatinase activities, even though FAP-a was independently identified in reactive stromal fibroblasts but not in tumor or endothelial cells. [6][7][8][9][10][11] In fact, seprase was found to be present on tumor cells of gastric, colon, melanoma, ovarian and breast cancers. [5][6][7][12][13][14][15] It is likely that activation, which involves the seprase dimer being shorn from the cell membrane to allow greater accessibility of its TICg substrate to the catalytic pore, is required prior to gelatinase activity. 16,17 Seprase is not only present on activated fibroblast during wound healing and active endothelial cells during angiogenesis, but also has been found to be constitutively expressed at high levels in some malignant melanoma, glioma and carcinoma cells; however, most epithelial tumor cell lines express little or no seprase (see gene expression profiles of NCI60 tumor cell lines http:// cgap.nci.nih.gov/Microarray/FNResults?O...

Among the many proteases associated with human cancer, seprase or fibroblast activation protein A, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTAsensitive activators, r-seprase was converted into 70-to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody-or lectinaffinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion. (Cancer Res 2006; 66(20): 9977-85)

Due to the low charge separation efficiency and high stability of the CO2 molecule, photoreduction of CO2 into a single multielectron product such as CH4 with a simultaneous high conversion rate and selectivity is challenging. Therefore, it is highly desirable to accelerate charge separation and transfer and provide an electron‐enriched catalyst surface for the deep reduction of CO2. Herein, a Pd/Cu2O/TiO2 ternary hybrid photocatalyst consisting of Pd nanoparticles (NPs) and Cu2O NPs‐decorated TiO2 nanosheets is rationally designed, and highly selective photocatalytic photoreduction of CO2 into CH4 is achieved. The Pd/Cu2O/TiO2 photocatalyst shows a high CH4 production rate of 42.8 μmol g−1 h−1 with an extremely high selectivity of 99.5%. This CH4 production rate is 61.1, 5.4, and 2.8 times higher than the bare TiO2, Cu2O/TiO2, and Pd/TiO2, respectively. In this Pd/Cu2O/TiO2 hybrid, a consecutive multistep charge transfer is steered between the Cu2O/TiO2 heterojunction and Pd, ensures accelerated charge separation and transfer, and leads to the formation of a spatially separated electron‐enriched surface (Pd) and hole‐enriched surface (Cu2O). This spatially oriented charge transfer and the charge‐enriched catalyst surface synergistically contribute to the simultaneous high conversion rate and selectivity of CH4.