Magdolen / Sommerhoff / Fritz Kallikrein-related peptidases

Vol. 2: Novel cancer-related biomarkers
1. Auflage 2012
ISBN: 978-3-11-030366-7
Verlag: De Gruyter
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band Volume 2, 241 Seiten

Reihe: Kallikrein-related peptidases

Various KLK proteins and their encoding genes have attracted increased attention among scientists and clinicians worldwide since they represent very interesting and functionally distinct biomarkers, particularly, in cancer. This book reviews the role of kallikrein-related peptidases (KLKs) in a wide range of cancers, including lung, prostate, breast and ovarian cancer. It provides clinicians, physician scientists and researchers with a comprehensive overview on the clinical relevance of KLK expression in various malignancies.

Zielgruppe

Researchers in Biochemistry, Molecular Biology, Molecular Medicine; Clinicians, Physician Scientists

Autoren/Hrsg.

Magdolen, Viktor

Sommerhoff, Christian P.

Fritz, Hans

Schmitt, Manfred

Fachgebiete

• Naturwissenschaften Biowissenschaften Molekularbiologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Vorklinische Medizin: Grundlagenfächer Molekulare Medizin, Zellbiologie
• Naturwissenschaften Biowissenschaften Biochemie (nichtmedizinisch)
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Klinische und Innere Medizin Onkologie, Krebsforschung

Inhaltsverzeichnis

1;Preface;5
2;List of contributing authors;7
3;Table of Contents;11
4;Introduction to Volume 2: Kallikrein-related Peptidases. Novel Cancer-related Biomarkers;17
4.1;Bibliography;18
5;1 Pathophysiology of Kallikrein-related Peptidases in Lung Cancer;19
5.1;1.1 Introduction;19
5.2;1.2 Expression pattern of KLKs in the normal lung;19
5.3;1.3 KLKs in lung cancer;22
5.4;1.4 Regulation of KLKs in the lung;24
5.4.1;1.4.1 Control of gene transcription;24
5.4.2;1.4.2 Post-translational control of KLK function;26
5.5;1.5 Potential KLK targets in the lung;27
5.5.1;1.5.1 Substrates involved in host defense;27
5.5.2;1.5.2 Cytokines and growth factors;29
5.5.3;1.5.3 Pericellular and membrane-associated substrates;32
5.6;1.6 Conclusion;34
5.7;Acknowledgements;35
5.8;Bibliography;35
6;2 Clinical Relevance of Kallikrein-related Peptidases in Gastric and Colorectal Cancer;43
6.1;2.1 Introduction;43
6.2;2.2 Features of gastric and colorectal cancers;43
6.3;2.3 Established biomarkers in gastric and colorectal cancer;44
6.4;2.4 KLKs: novel biomarkers in gastric and colorectal cancer;46
6.4.1;2.4.1 Review of the clinical relevance of KLK expression in gastric cancer;47
6.4.2;2.4.2 Review of the clinical relevance of KLK expression in colorectal cancer;51
6.5;2.5 Proteolytic activity of KLKs in gastric/colorectal cancers;54
6.6;2.6 Effect of KLK expression on cell regulation and metabolic pathways;55
6.7;2.7 Conclusion;56
6.8;Bibliography;56
7;3 Pathophysiology of Kallikrein-related Peptidases in Head and Neck Cancer;61
7.1;3.1 Introduction;61
7.2;3.2 A murine orthotopic xenograft model using urinary-type plasminogen activator receptor (uPAR) overexpressing OSCC cells mimics aggressive human OSCC;63
7.3;3.3 Expression of KLKs in OSCC;65
7.4;3.4 Potential functional role of KLK5 in regulating cell-cell junctional integrity in OSCC;66
7.5;3.5 Conclusions and future directions;70
7.6;Acknowledgement;71
7.7;Bibliography;71
8;4 PSA (Prostate-Specific Antigen) and other Kallikrein-related Peptidases in Prostate Cancer;77
8.1;4.1 Introduction;77
8.2;4.2 The role of KLKs in prostate cancer diagnosis, prognosis and monitoring;77
8.2.1;4.2.1 PSA;77
8.2.2;4.2.2 KLK2;81
8.2.3;4.2.3 Other KLKs;81
8.2.4;4.2.4 Splicing and polymorphic variants;82
8.3;4.3 Potential functional roles of KLKs in prostate cancer;82
8.3.1;4.3.1 Sustaining proliferative signaling and evading growth suppressors;83
8.3.2;4.3.2 Resisting cell death;85
8.3.3;4.3.3 Inducing angiogenesis;85
8.3.4;4.3.4 Activating invasion and metastasis;87
8.3.5;4.3.5 Concerns about biological studies;88
8.4;4.4 Conclusions and outlook;88
8.5;Bibliography;89
9;5 Cellular Model Systems to Study the Tumor Biological Role of Kallikrein-related Peptidases in Ovarian and Prostate Cancer;99
9.1;5.1 Introduction;99
9.2;5.2 Development of cellular model systems in cancer research;99
9.3;5.3 Traditional 3D cellular models commonly used in both ovarian and prostate cancers;100
9.3.1;5.3.1 Soft agar colony assay;100
9.3.2;5.3.2 3D-Matrigel™;101
9.4;5.4 Novel 3D cellular models in ovarian cancer biology;102
9.4.1;5.4.1 Ovarian cancer;102
9.4.2;5.4.2 3D-suspension model to mimic ascites suspension;102
9.4.3;5.4.3 In vitro models for ovarian cancer invasion into the peritoneal membrane;106
9.4.4;5.4.4 The role of 3D-collagen I matrix in ovarian cancer cell behavior;108
9.4.5;5.4.5 A 3D-organotypic model to mimic ovarian cancer metastasis;108
9.4.6;5.4.6 Bioengineered 3D culture systems for ovarian cancer;109
9.5;5.5 Cellular models in prostate cancer;111
9.5.1;5.5.1 Prostate cancer;111
9.5.2;5.5.2 3D-suspension models for prostate cancer growth and metastasis;113
9.5.3;5.5.3 In vitro models for prostate cancer angiogenesis;114
9.5.4;5.5.4 Bioengineered 3D culture systems for prostate cancer growth and metastasis;114
9.6;5.6 Challenges and future direction;118
9.7;Acknowledgment;118
9.8;Bibliography;119
10;6 Clinical Relevance of Kallikrein-related Peptidases in Breast Cancer;127
10.1;6.1 Introduction;127
10.2;6.2 Expression of KLKs in normal breast tissue;129
10.3;6.3 Clinical relevance of KLKs in breast cancer;129
10.4;6.4 Hormonal regulation of KLKs in breast cancer;143
10.5;6.5 Tumor suppressor role of KLKs in breast cancer;145
10.6;6.6 DNA-methylation of KLKs as the basis of KLK downregulation in breast cancer;146
10.7;6.7 Conclusions;148
10.8;Bibliography;148
11;7 Clinical Relevance of Kallikrein-related Peptidases in Ovarian Cancer;161
11.1;7.1 Introduction;161
11.2;7.2 Ovarian cancer pathology, diagnosis, and therapy;161
11.3;7.3 KLKs in ovarian cancer;163
11.3.1;7.3.1 Circulating KLKs as screening/diagnostic and/or prognostic ovarian cancer biomarkers;164
11.3.2;7.3.2 Serum ovarian cancer biomarkers CA125 and KLKs;171
11.3.3;7.3.3 Tumor tissue-associated KLKs as prognostic ovarian cancer biomarkers;172
11.4;7.4 Tumor tissue-associated and blood-borne KLKs as predictive ovarian cancer biomarkers;173
11.5;7.5 Conclusion;174
11.6;Abbreviations;175
11.7;Bibliography;176
12;8 microRNAs: A New Control Mechanism for Kallikrein-related Peptidases in Kidney and Other Cancers;183
12.1;8.1 Introduction;183
12.1.1;8.1.1 KLK expression in normal kidney tissue;183
12.1.2;8.1.2 KLKdysregulation in kidney cancer;184
12.2;8.2 microRNAs (miRNA);185
12.2.1;8.2.1 Biogenesis;185
12.2.2;8.2.2 miRNAs and cancer;186
12.2.3;8.2.3 miRNA dysregulation in renal cell carcinoma;186
12.2.4;8.2.4 The miRNA-KLK interaction;187
12.3;8.3 miRNA control of KLK expression in renal cell carcinoma;190
12.4;8.4 miRNA control of KLK expression in other cancers;191
12.5;8.5 Conclusions and outlook;192
12.6;Bibliography;193
13;9 Genomic Instability of the KLK-locus in Cancer;199
13.1;9.1 Introduction;199
13.2;9.2 Defining genomic instability;199
13.2.1;9.2.1 Defining CIN and its underlying mechanisms;200
13.2.2;9.2.2 Methods for detecting CIN;201
13.3;9.3 Chromosome 19 and the KLK locus in cancer;202
13.3.1;9.3.1 Chromosome 19;202
13.3.2;9.3.2 The KLK locus and cancer;203
13.3.3;9.3.3 KLK sequence mutations and single nucleotide polymorphisms in cancer;204
13.3.4;9.3.4 KLK translocations;205
13.3.5;9.3.5 Copy-number changes of the KLK locus;207
13.4;9.4 Closing remarks;209
13.5;Bibliography;210
14;10 Kallikrein-related Peptidases as Biomarkers in Personalized Cancer Medicine;217
14.1;10.1 Introduction;217
14.2;10.2 The role of KLKs as cancer biomarkers for predicting and monitoring response to chemotherapy or endocrine therapy;220
14.2.1;10.2.1 Prostate cancer;222
14.2.2;10.2.2 Breast cancer;223
14.2.3;10.2.3 Ovarian cancer;223
14.3;10.3 Modulation of expression levels of KLK genes upon chemotherapy administration in vitro;225
14.3.1;10.3.1 Prostate cancer cells;226
14.3.2;10.3.2 Gastric cancer cells;226
14.3.3;10.3.3 Breast cancer cells;227
14.3.4;10.3.4 The role of microRNAs (miRNAs) that target KLK expression and the methylation status of KLK genes in the in vitro response of cancer cells to chemotherapy;228
14.4;10.4 Conclusions and future directions;229
14.5;Bibliography;230
15;Index;235

Über Autor(innen)

Viktor Magdolen, Technical University Munich; Christian Sommerhoff and Hans Fritz, Ludwig Maximilian University, Munich; Manfred Schmitt, Technical University Munich, Germany.