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CYTOKERATINS –

TOOLS IN ONCOLOGY

Edited by Gerhard Hamilton

Cytokeratins – Tools in Oncology

Edited by Gerhard Hamilton

Published by InTech

Janeza Trdine 9, 51000 Rijeka, Croatia

Copyright © 2012 InTech

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Statements and opinions expressed in the chapters are these of the individual contributors

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Publishing Process Manager Martina Durovic

Technical Editor Teodora Smiljanic

Cover Designer InTech Design Team

First published February, 2012

Printed in Croatia

A free online edition of this book is available at www.intechopen.com

Additional hard copies can be obtained from [email protected]

Cytokeratins – Tools in Oncology, Edited by Gerhard Hamilton

p. cm.

ISBN 978-953-51-0047-8

Contents

Preface IX

Part 1 Expression of Cytokeratins in Nonmalignant Tissue 1

Chapter 1 The Expression of Cytokeratins in Bovine

Intestinal Microfold (M) Cells 3

Takashi Kanaya, Tetsuya Hondo, Kohtaro Miyazawa,

Michael T. Rose and Hisashi Aso

Chapter 2 Cytokeratins of the Liver and Intestine Epithelial

Cells During Development and Disease 15

Priti Chougule and Suchitra Sumitran-Holgersson

Part 2 Expression of Cytokeratins in Malignant Tissues 33

Chapter 3 Epithelial to Mesenchymal Transition in

Microbial Pathogenesis 35

Abderrahman Chargui, Mimouna Sanda,

Patrick Brest, Paul Hofman and Vouret-Craviari Valérie

Chapter 4 Cytokeratin 7 and 20 55

Agnieszka Jasik

Chapter 5 Cytokeratin 8: The Dominant Type II

Intermediate Filament Protein in Lung Cancer 67

Nobuhiro Kanaji, Akihito Kubo, Shuji Bandoh, Tomoya Ishii,

Jiro Fujita, Takuya Matsunaga and Etsuro Yamaguchi

Part 3 Cytokeratins as Markers of Tumor

Dissemination and Response 97

Chapter 6 Cytokeratin 18 (CK18) and CK18

Fragments for Detection of Minimal

Residual Disease in Colon Cancer Patients 99

Ulrike Olszewski-Hamilton, Veronika Buxhofer-Ausch,

Christoph Ausch and Gerhard Hamilton

VI Contents

Chapter 7 FISH Probe Counting in Circulating Tumor Cells 119

Sjoerd T. Ligthart, Joost F. Swennenhuis,

Jan Greve and Leon W.M.M. Terstappen

Chapter 8 Cytokeratin 18 (CK18) and Caspase-Cleaved CK18 (ccCK18)

as Response Markers in Anticancer Therapy 135

Hamilton Gerhard

Preface

The present volume “Cytokeratins – Tools in Oncology” is a new addition to the

Intech collection of books that aims at providing scientists and clinicians with a

comprehensive overview of specific aspects of the latest research and current

knowledge related to the application of cytokeratins in histology, cancer research and

clinical diagnosis of tumors. For this purpose a series of research articles, clinical

investigations and reviews that deal with the role of the most abundant cytokeratin

types in normal and malignant tissues were included. This volume aptly adds to the

other Intech titles in the field of oncology, particularly describing advances in cancer

therapy, diagnosis and treatment of individual tumor entities as well as the important

topic of cancer stem cells.

The participating authors shared their expertise about the multiple functions of

cytokeratins in organization of the intermediary filaments in normal intestine and liver

as well as microfold L cells and, furthermore, the usability of cytokeratins 7, 8, and 20

in tumor diagnosis. Epithelial to mesenchymal transition as a mechanism important in

pathogenesis is touched in another chapter, followed by several articles discussing the

assessment of cytokeratins in disseminated tumor cells and as response markers

during chemotherapy. Our group published reports on the use of cytokeratin

fragments in prostate cancer patients undergoing intermittent androgen suppression

in the late nineties and it was fascinating to observe the continuative development of

anti-cytokeratin reagents as diagnostic and possible predictive tools available in the

form of refined assays providing highly valuable means to detect the presence of

disseminated tumor cells and minimal residual disease in cancer patients. This book is

therefore destined to all cancer researchers and therapists who want to understand the

diagnostic use of cytokeratins in histology and especially to tackle the challenge of

finding residual tumor cells in patients, either circulating in the blood or residing

hidden in niches, that may lead to tumor recurrence and qualify patients for a more

aggressive anticancer therapy.

As editor of this book, I would like to acknowledge the significant efforts made by all

of the contributing authors and the entire editorial team in publishing of this work. I

would like to dedicate this book to the “Ludwig Boltzmann Society” and, in particular,

to Prof. Dr. Gerhard Baumgartner whose long-standing support has allowed for the

X Preface

successful realization of many scientific projects. Last but not least, I would like to

thank my wife for her personal support and great patience at all times.

Gerhard Hamilton, PhD

Ludwig Boltzmann Cluster of Translational Oncology, Vienna,

Austria

Part 1

Expression of Cytokeratins in

Nonmalignant Tissue

1

The Expression of Cytokeratins

in Bovine Intestinal Microfold (M) Cells

Takashi Kanaya1, Tetsuya Hondo1,

Kohtaro Miyazawa1, Michael T. Rose2 and Hisashi Aso1

1Tohoku University 2Aberystwyth University,

1Japan

2UK

1. Introduction

The mucosal surface of the gut is exposed to a variety of foreign antigens and

microorganisms, some of which are potentially harmful for the host. To protect against the

risk of infection, the intestinal mucosa has developed specialized organized lymphoid

tissues and epithelial cells. The gut-associated lymphoid tissues (GALT) including Peyer’s

patches (PPs) are major inductive sites for intestinal immunity. Different from other

peripheral lymphoid tissues, GALT lacks afferent lymphatics, and directly samples mucosal

antigens across the epithelial barrier to initiate antigen-specific immune responses. This task

is accomplished by specialized epithelial cells within the follicle-associated epithelium

(FAE) covering the lymphoid follicles of GALT known as microfold (M) cells.

M cells possess a high capacity for phagocytosis and transcytosis, and these functions allow

the rapid transport of antigens into the underlying lymphoid tissues, especially antigen￾presenting cells. Antigens are then presented to T cells that support B-cell activation, resulting

ultimately in the generation of IgA-producing plasma cells. Thus, M-cell-mediated antigen

transport is important for the initiation of mucosal immune responses (Kraehenbuhl and

Neutra, 2000; Neutra et al., 1996; Neutra et al., 2001). In order to express their specialized

functions including phagocytosis and transcytosis, M cells exhibit unique morphologies that

differ from the surrounding absorptive enterocytes. M cells lack a dense microvilli brush

border structure, though they do possess shorter and irregular microvilli on their apical

surface. On the basolateral side, a pocket-like invagination of the plasma membrane is formed

to house lymphocytes and antigen-presenting cells (Neutra et al., 1996).

These morphological features of M cells have an effect on the composition of the cytoskeletal

proteins within the cell, such as actin-containing microfilaments, intermediate filaments and

their associated proteins. For example, the lack of a brush border in M cells is reflected in the

cellular localization of the actin and villin, resulting in unusual staining patterns of these

proteins in M cells of mice and calves, as actin and villin are essential proteins for microvilli

formation (Kanaya et al., 2007; Kerneis et al., 1996). In addition to the abnormal cellular

localization of actin and actin-related proteins, some investigators have demonstrated that

intermediate filament proteins such as vimentin and cytokeratins can be used as