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.
Author(s): Viktor Magdolen, Christian P. Sommerhoff, Hans Fritz, Manfred Schmitt
Publisher: de Gruyter
Year: 2012
Language: English
Pages: XVI+226
Kallikrein-related peptidases, Volume 2: Novel cancer-related biomarkers......Page 4
Preface......Page 6
List of contributing authors......Page 8
Table of Contents......Page 12
Introduction to Volume 2: Kallikrein-related Peptidases. Novel Cancer-related Biomarkers......Page 18
Bibliography......Page 19
1.2 Expression pattern of KLKs in the normal lung......Page 20
1.3 KLKs in lung cancer......Page 23
1.4.1 Control of gene transcription......Page 25
1.4.2 Post-translational control of KLK function......Page 27
1.5.1 Substrates involved in host defense......Page 28
1.5.2 Cytokines and growth factors......Page 30
1.5.3 Pericellular and membrane-associated substrates......Page 33
1.6 Conclusion......Page 35
Bibliography......Page 36
2.2 Features of gastric and colorectal cancers......Page 44
2.3 Established biomarkers in gastric and colorectal cancer......Page 45
2.4 KLKs: novel biomarkers in gastric and colorectal cancer......Page 47
2.4.1 Review of the clinical relevance of KLK expression in gastric cancer......Page 48
2.4.2 Review of the clinical relevance of KLK expression in colorectal cancer......Page 52
2.5 Proteolytic activity of KLKs in gastric/colorectal cancers......Page 55
2.6 Effect of KLK expression on cell regulation and metabolic pathways......Page 56
Bibliography......Page 57
3.1 Introduction......Page 62
3.2 A murine orthotopic xenograft model using urinary-type plasminogen activator receptor (uPAR) overexpressing OSCC cells mimics aggressive human OSCC......Page 64
3.3 Expression of KLKs in OSCC......Page 66
3.4 Potential functional role of KLK5 in regulating cell-cell junctional integrity in OSCC......Page 67
3.5 Conclusions and future directions......Page 71
Bibliography......Page 72
4.2.1 PSA......Page 78
Different molecular forms of PSA......Page 80
4.2.3 Other KLKs......Page 82
4.3 Potential functional roles of KLKs in prostate cancer......Page 83
4.3.1 Sustaining proliferative signaling and evading growth suppressors......Page 84
4.3.3 Inducing angiogenesis......Page 86
4.3.4 Activating invasion and metastasis......Page 88
4.4 Conclusions and outlook......Page 89
Bibliography......Page 90
5.2 Development of cellular model systems in cancer research......Page 100
5.3.1 Soft agar colony assay......Page 101
5.3.2 3D-Matrigel™......Page 102
5.4.2 3D-suspension model to mimic ascites suspension......Page 103
5.4.3 In vitro models for ovarian cancer invasion into the peritoneal membrane......Page 107
5.4.5 A 3D-organotypic model to mimic ovarian cancer metastasis......Page 109
5.4.6 Bioengineered 3D culture systems for ovarian cancer......Page 110
5.5.1 Prostate cancer......Page 112
5.5.2 3D-suspension models for prostate cancer growth and metastasis......Page 114
5.5.4 Bioengineered 3D culture systems for prostate cancer growth and metastasis......Page 115
Acknowledgment......Page 119
Bibliography......Page 120
6.1 Introduction......Page 128
6.3 Clinical relevance of KLKs in breast cancer......Page 130
6.4 Hormonal regulation of KLKs in breast cancer......Page 144
6.5 Tumor suppressor role of KLKs in breast cancer......Page 146
6.6 DNA-methylation of KLKs as the basis of KLK downregulation in breast cancer......Page 147
Bibliography......Page 149
7.2 Ovarian cancer pathology, diagnosis, and therapy......Page 162
7.3 KLKs in ovarian cancer......Page 164
7.3.1 Circulating KLKs as screening/diagnostic and/or prognostic ovarian cancer biomarkers......Page 165
7.3.2 Serum ovarian cancer biomarkers CA125 and KLKs......Page 172
7.3.3 Tumor tissue-associated KLKs as prognostic ovarian cancer biomarkers......Page 173
7.4 Tumor tissue-associated and blood-borne KLKs as predictive ovarian cancer biomarkers......Page 174
7.5 Conclusion......Page 175
Abbreviations......Page 176
Bibliography......Page 177
8.1.1 KLK expression in normal kidney tissue......Page 184
8.1.2 KLK dysregulation in kidney cancer......Page 185
8.2.1 Biogenesis......Page 186
8.2.3 miRNA dysregulation in renal cell carcinoma......Page 187
8.2.4 The miRNA-KLK interaction......Page 188
8.3 miRNA control of KLK expression in renal cell carcinoma......Page 191
8.4 miRNA control of KLK expression in other cancers......Page 192
8.5 Conclusions and outlook......Page 193
Bibliography......Page 194
9.2 Defining genomic instability......Page 200
9.2.1 Defining CIN and its underlying mechanisms......Page 201
9.2.2 Methods for detecting CIN......Page 202
9.3.1 Chromosome 19......Page 203
9.3.2 The KLK locus and cancer......Page 204
9.3.3 KLK sequence mutations and single nucleotide polymorphisms in cancer......Page 205
9.3.4 KLK translocations......Page 206
9.3.5 Copy-number changes of the KLK locus......Page 208
9.4 Closing remarks......Page 210
Bibliography......Page 211
10.1 Introduction......Page 218
10.2 The role of KLKs as cancer biomarkers for predicting and monitoring response to chemotherapy or endocrine therapy......Page 221
10.2.1 Prostate cancer......Page 223
10.2.3 Ovarian cancer......Page 224
10.3 Modulation of expression levels of KLK genes upon chemotherapy administration in vitro......Page 226
10.3.2 Gastric cancer cells......Page 227
10.3.3 Breast cancer cells......Page 228
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......Page 229
10.4 Conclusions and future directions......Page 230
Bibliography......Page 231
Index......Page 236
