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serine protease cancer

Petr Busek, Rosana Mateu, Michal Zubal, Lenka Kotackova, Aleksi Sedo
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
Ning Xia, Dehua Deng, Yiru Wang, Chao Fang, Su-Juan Li
Background: Prostate-specific antigen (PSA), a serine protease, is a biomarker for preoperative diagnosis and screening of prostate cancer and monitoring of its posttreatment. Methods: In this work, we reported a colorimetric method for clinical detection of PSA using gold nanoparticles (AuNPs) as the reporters. The method is based on ascorbic acid (AA)-induced in situ formation of AuNPs and Cu2+ -catalyzed oxidation of AA. Specifically, HAuCl4 can be reduced into AuNPs by AA; Cu2+ ion can catalyze the oxidation of AA by O2 to inhibit the formation of AuNPs...
2018: International Journal of Nanomedicine
Rhiannon L Harries, Sioned Owen, Fiona Ruge, Meleri Morgan, Jun Li, Zhangtao Zhang, Keith G Harding, Jared Torkington, Wen G Jiang, Jun Cai
Pigment epithelial derived factor (PEDF) is a secreted glycoprotein that is a non-inhibitory member of the serine protease inhibitor (serpin) family. PEDF exhibits multiple biological properties including neuroprotective, anti-angiogenic, and immune-modulating. Interestingly, PEDF exerts the inhibitory effects in cancers derived from certain tissues, including prostatic, ovarian, and pancreatic carcinomas. The current study aimed to elucidate its role in colorectal cancer development. PEDF expression in human colorectal cancer tissue was assessed using quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC)...
April 10, 2018: Oncotarget
Ellen Puré, Rachel Blomberg
Fibroblast activation protein (FAP) is a cell-surface serine protease that acts on various hormones and extracellular matrix components. FAP is highly upregulated in a wide variety of cancers, and is often used as a marker for pro-tumorigenic stroma. It has also been proposed as a molecular target of cancer therapies, and, especially in recent years, a great deal of research has gone into design and testing of diverse FAP-targeted treatments. Yet despite this growing field of research, our knowledge of FAP's basic biology and functional roles in various cancers has lagged behind its use as a tumor-stromal marker...
May 3, 2018: Oncogene
Aneta A Koronowicz, Mariola Drozdowska, Paula Banks, Ewelina Piasna-Słupecka, Dominik Domagała, Teresa Leszczyńska
BACKGROUND: Fatty acids from conjugated linoleic acid (CLA)-enriched egg yolk suppressed the viability of the MCF-7 cancer line more effectively than non-enriched egg yolk. Herein we aimed to determine the molecular mechanisms by analysing the expression and activation of proteins involved in cellular stress and apoptosis signaling. MATERIALS AND METHODS: Forty-eight Isa Brown laying hens (26-week-old) were fed a fortified (0.75% CLA) or a control diet (0% CLA) for 4 months...
May 2018: Anticancer Research
Ralph Klose, M Gordian Adam, Eva-Maria Weis, Iris Moll, Joycelyn Wüstehube-Lausch, Fabian Tetzlaff, Chio Oka, Michael Ehrmann, Andreas Fischer
The serine protease HTRA1 is involved in several vascular diseases and its expression is often deregulated in cancer. We aimed at identifying how HTRA1 in the vasculature affects tumor growth. Here we report that silencing of HTRA1 in cultured endothelial cells increased migration rate and tube formation, whereas forced HTRA1 expression impaired sprouting angiogenesis. Mechanistically, endothelial HTRA1 expression enhanced Delta/Notch signaling by reducing the amount of the weak Notch ligand JAG1. HTRA1 physically interacted with JAG1 and cleaved it within the intracellular domain, leading to protein degradation...
May 1, 2018: Oncogene
Marta Zarà, Ilaria Canobbio, Caterina Visconte, Jessica Canino, Mauro Torti, Gianni Francesco Guidetti
Tumor cell-induced platelet aggregation represents a critical process both for successful metastatic spread of the tumor and for the development of thrombotic complications in cancer patients. To get further insights into this process, we investigated and compared the molecular mechanisms of platelet aggregation induced by two different breast cancer cell lines (MDA-MB-231 and MCF7) and a colorectal cancer cell line (Caco-2). All the three types of cancer cells were able to induce comparable platelet aggregation, which, however, was observed exclusively in the presence of CaCl2 and autologous plasma...
April 26, 2018: Cellular Signalling
Jack D Stopa, Jeffrey I Zwicker
The mechanisms underlying the hypercoagulability of cancer are complex and include the upregulation coagulation factors or procoagulant proteins, shedding of microparticles, and direct activation of vascular cells. Protein disulfide isomerase (PDI) is a thiol isomerase secreted from activated platelets and endothelial cells and plays a critical role in both platelet aggregation and fibrin generation. A number of potential intravascular targets of PDI have been identified including cell surface receptors (e...
April 2018: Thrombosis Research
Alexander Zwirzitz, Michael Reiter, Rostislav Skrabana, Anna Ohradanova-Repic, Otto Majdic, Marianna Gutekova, Ondrej Cehlar, Eva Petrovčíková, Eva Kutejova, Gerold Stanek, Hannes Stockinger, Vladimir Leksa
The plasminogen system is essential for dissolution of fibrin clots, and in addition, it is involved in a wide variety of other physiological processes, including proteolytic activation of growth factors, cell migration, and removal of protein aggregates. On the other hand, uncontrolled plasminogen activation contributes to many pathological processes, e.g. tumor cells' invasion in cancer progression. Moreover, some virulent bacterial species, e.g. Streptococci or Borrelia, bind human plasminogen and hijack the host's plasminogen system to penetrate tissue barriers...
April 18, 2018: Journal of Biological Chemistry
Maya B Kostova, William Nathaniel Brennen, David Lopez, Lizamma Anthony, Hao Wang, Elizabeth Platz, Samuel R Denmeade
BACKGROUND: Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured...
April 16, 2018: Prostate
Angélica Aponte-López, Ezequiel M Fuentes-Pananá, Daniel Cortes-Muñoz, Samira Muñoz-Cruz
Mast cells are unique tissue-resident immune cells that secrete a diverse array of biologically active compounds that can stimulate, modulate, or suppress the immune response. Although mounting evidence supports that mast cells are consistently infiltrating tumors, their role as either a driving or an opposite force for cancer progression is still controversial. Particularly, in breast cancer, their function is still under discussion. While some studies have shown a protective role, recent evidence indicates that mast cells enhance blood and lymphatic vessel formation...
2018: Journal of Immunology Research
Ronak Tilvawala, Son Hong Nguyen, Aaron J Maurais, Venkatesh V Nemmara, Mitesh Nagar, Ari J Salinger, Sunil Nagpal, Eranthie Weerapana, Paul R Thompson
Increased protein citrullination is linked to various diseases including rheumatoid arthritis (RA), lupus, and cancer. Citrullinated autoantigens, a hallmark of RA, are recognized by anti-citrullinated protein antibodies (ACPAs) which are used to diagnose RA. ACPA-recognizing citrullinated enolase, vimentin, keratin, and filaggrin are also pathogenic. Here, we used a chemoproteomic approach to define the RA-associated citrullinome. The identified proteins include numerous serine protease inhibitors (Serpins), proteases and metabolic enzymes...
March 21, 2018: Cell Chemical Biology
Xiao-Yan Cao, Xiao-Xin Zhang, Min-Wei Yang, Li-Peng Hu, Shu-Heng Jiang, Guang-Ang Tian, Li-Li Zhu, Qing Li, Yong-Wei Sun, Zhi-Gang Zhang
Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC...
April 2, 2018: Biochemical and Biophysical Research Communications
Anastasia Chillà, Francesca Margheri, Alessio Biagioni, Mario Del Rosso, Gabriella Fibbi, Anna Laurenzana
BACKGROUND: Controlling vascular growth is a challenging aim for the inhibition of tumor growth and metastasis. The amoeboid and mesenchymal types of invasiveness are two modes of migration interchangeable in cancer cells: the Rac-dependent mesenchymal migration requires the activity of proteases; the Rho-ROCK-dependent amoeboid motility is protease-independent and has never been described in endothelial cells. METHODS: A cocktail of physiologic inhibitors (Ph-C) of serine-proteases, metallo-proteases and cysteine-proteases, mimicking the physiological environment that cells encounter during their migration within the angiogenesis sites was used to induce amoeboid style migration of Endothelial colony forming cells (ECFCs) and mature endothelial cells (ECs)...
April 3, 2018: Journal of Experimental & Clinical Cancer Research: CR
Panagiotis G Adamopoulos, Christos K Kontos, Andreas ScorilasP
Tissue kallikrein, kallikrein-related peptidases (KLKs), and plasma kallikrein form the largest group of serine proteases in the human genome, sharing many structural and functional properties. Several KLK transcripts have been found aberrantly expressed in numerous human malignancies, confirming their prognostic or/and diagnostic values. However, the process of alternative splicing can now be studied in-depth due to the development of Next-Generation Sequencing (NGS). In the present study, we used NGS to discover novel transcripts of the KLK1 and KLK2 genes, after nested touchdown PCR...
March 31, 2018: Genomics
Woodys Lenga Ma Bonda, Sophie Iochmann, Mélia Magnen, Yves Courty, Pascale Reverdiau
Human tissue kallikreins (KLKs) are 15 members of the serine protease family and are present in various healthy human tissues including airway tissues. Multiple studies have revealed their crucial role in the pathophysiology of a number of chronic, infectious and tumour lung diseases. KLK1, 3 and 14 are involved in asthma pathogenesis, and KLK1 could be also associated with the exacerbation of this inflammatory disease caused by rhinovirus. KLK5 was demonstrated as an influenza virus activating protease in humans, and KLK1 and 12 could also be involved in the activation and spread of these viruses...
March 1, 2018: Biological Chemistry
Ashley Di Meo, Cong Wang, Yufeng Cheng, Eleftherios P Diamandis, George M Yousef
The kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs have been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3' untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney, and ovarian cancers...
March 1, 2018: Biological Chemistry
Dustin B Manders, Hari Annavarapu Kishore, Adi F Gazdar, Patrick W Keller, Jun Tsunezumi, Hiromi Yanagisawa, Jayanthi Lea, Ruth Ann Word
Fibulin 5 (FBLN5) is an extracellular matrix glycoprotein that suppresses matrix metalloprotease 9 (MMP-9), angiogenesis and epithelial cell motility. Here, we investigated the regulation and function of FBLN5 in epithelial ovarian cancer (EOC). FBLN5 mRNA was down-regulated 5-fold in EOC relative to benign ovary. Not surprisingly, MMP9 mRNA and enzyme activity were increased significantly, and inversely correlated with FBLN5 gene expression. FBLN5 degradation products of 52.8 and 41.3 kDa were increased substantially in EOC...
March 6, 2018: Oncotarget
Diana Cristina Pérez-Ibave, Carlos Horacio Burciaga-Flores, Miguel-Ángel Elizondo-Riojas
Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men...
March 23, 2018: Cancer Epidemiology
Rishi Kumar Jaiswal, Akhil Kumar Varshney, Pramod Kumar Yadava
The urokinase plasminogen activator system is a family of serine proteases which consists of uPA (urokinase plasminogen activator), uPAR (urokinase type plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1). In addition to their significant roles in activation, these proteases act as key regulators of the tumor microenvironment and are involved in the metastatic process in many cancers. High levels of uPA system proteases in many human cancer predicts poor patient prognosis and strongly indicated a key role of uPA system in cancer metastasis...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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