Cell adhesion and communication mediated by the CEA family : basic and clinical perspectives

337 Pages·1998·6.666 MB·English

by  Stanners, Clifford P

CELL ADHESION AND
COMMUNICATION MEDIATED BY
THE CEA FAMILY
Cell Adhesion and Communication
A series of books encompassing monographs on classes of adhesion molecules and
monographs giving a broader functional synopsis on adhesion molecules on a
particular system.
Edited by Christo Goridis
Volume 1
Cell Adhesion Molecules in Cancer and Inflammation
edited by A.A.Epenetos and M.Pignatelli
Volume 2
The Laminins
edited by P.Ekblom and R.Timpl
Volume 3
Tenascin and Counteradhesive Molecules of the Extracellular Matrix
edited by K.L.Crossin
Volume 4
Adhesion Molecules and Chemokines in Lymphocyte Trafficking
edited by A.Hamann
Volume 5
Cell Adhesion and Communication Mediated by the CEA Family
Basic and Clinical Perspectives
edited by C.P.Stanners
Other volumes in preparation
Ig Superfamily Adhesion Molecules
edited by P.Sonderegger
Epithelial Morphogenesis in Development and Disease
edited by W.Birchmeier and C.Birchmeier
Cell Adhesion Molecules in the Skin
edited by J.N.W.N.Barker and J.McGrath
This book is part of a series. The publisher will accept continuation orders which
may be cancelled at any time and which provide for automatic billing and
shipping of each title in the series upon publication. Please write for details.
CELL ADHESION AND
COMMUNICATION
MEDIATED BY THE CEA
FAMILY
Basic and Clinical Perspectives
Edited by
Clifford P.Stanners
Biochemistry Department
McGill Cancer Centre
McGill University
Montreal
Canada
harwood academic publishers
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Copyright © 1998OPA (Overseas Publishers Association) Amsterdam B.V. Published
under license under the Harwood Academic Publishers imprint, part of The Gordon and
Breach Publishing Group.
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storage or retrieval system, without permission in writing from the publisher. Printed in
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British Library Cataloguing in Publication Data
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ISBN: 90-5702-290-7 (Print Edition)
CONTENTS
Preface to the series vii
Introduction ix
Contributors xiv
1. The Nature and Expression of the Human CEA Family 1
S.Hammarström, A.Olsen, S.Teglund and V.Baranov
2. The Nature and Expression of the Rodent CEA Families: 33
Evolutionary Considerations
W.Zimmermann
3. Properties of Adhesion Mediated by the Human CEA Family 59
C.P.Stanners and A.Fuks
4. Cell Adhesion and Signaling by the Rodent CEA Family 75
B.Öbrink and I.Hunter
5. CEA Family Members Expressed on Hematopoietic Cell and their 103
Possible Role in Cell Adhesion and Signaling
F.Grunert, M.Kuroki and S.C.Stocks
6. Signal Transduction Mediated by the CEA Family 125
P.Dr áber and K.M.Skubitz
7. Contributions of the Human CEA Family to Malignant 146
Transformation
C.P.Stanners
8. Role of C-CAM as a Tumor Suppressor 161
N.Beauchemin and S.-H.Lin
9. Rodent CEA-Related Glycoproteins are Receptors for Murine 183
Coronaviruses
K.V.Holmes and G.S.Dveksler
10. CEA and Metastasis: A Facilitator of Site-Specific Metastasis 201
J.M.Jessup and P.Thomas
11. Carcinoembryonic Antigen (CEA) a Model for Immunotherapy 230
using Recombinant Vaccines
J.W.Hodge and J.Schlom
vi
12. Novel Clinical Applications of CEA in Cancer Imaging and Therapy 245
with Radiolabeled Antibodies
D.M.Goldenberg, R.M.Sharkey, T.M.Behr and M.Juweid
13. Mice Transgenic for the CEA Gene as a Model for Cancer 277
Immunotherapy and Antibody Targeting Studies
F.J.Primus, J.Mann, G.Szalai, S.Wetzel, S.Mizobata, J.F.Simpson and
P.Clarke
14. The CEA Gene Promoter as a Driver of Tumor-Specific Gene 299
Expression for Gene Therapy
J.Thompson
Index 314
PREFACE TO THE SERIES
The development and normal functioning of all multicellular organisms is governed
to a large part by the interactions cells undergo with neighboring cells and with their
acellular environment. Many of these interactions are mediated by cell-cell adhesion
molecules and by extracellular matrix components and their cellular receptors, that is
by molecules which establish direct cell-cell and cell-matrix contacts. These
molecules are particularly important for determining whether a cell remains where it
is or moves elsewhere and, if a cell moves, where it goes and when it stops
migrating. These are of course key events during normal development, but they play
equally crucial roles in adult physiology and pathology, such as the extravasation of
white blood cells, inflammatory processes and wound healing, tumour invasiveness
and metastasis. Moreover, recent advances in the field show that most, if not all, cell
adhesion molecules are capable of triggering intracellular events, in the same way as
diffusible growth and differentiation factors and their cellular receptors do. It is thus
hardly surprising that clinicians are devoting increasing attention to the molecular
mechanisms underlying cell adhesion, and that cell adhesion molecules are now being
considered as suitable targets for drug development.
This book series is aimed at scientists, both in academia and in industry, and at
graduate students planning to move into the area, at the clinician, who wants to
become familiar with a field with many clinical implications, at scientists already
working in the field, who want to keep abreast with the recent developments outside
their own speciality. Hence, each volume of the series provides a review of a
particular segment of the field as well as critical assessment of recent discoveries and
future developments. Each volume has a volume editor, who is an expert in the field
and invites contributors to cover the different aspects of the topic. By keeping the
number of contributors to each volume small, we hope to avoid overlaps and
redundancies, common pitfalls of multi-author volumes. By looking at the previous
volumes, I have the impression that we have been successful.
One part of the series concentrates on important structural families of molecules,
another one addresses the role of cell adhesion in selected physiological and
pathological phenomena. The volumes on Cell Adhesion Molecules in Cancer and
viii
Inflammation and on Adhesion Molecules andChemokines in Lymphocyte Trafficking are
examples of the second; the present volume is an excellent example of the first kind.
It deals with the carcinoembryonic antigen family of molecules, an intriguing
structural family of cell adhesion molecules well known to the clinician for their
occurrence in the blood of patients suffering from a variety of different cancers. The
book combines reviews of our current knowledge on the normal expression,
physiological function and evolution of this gene family with chapters on clinical
applications. In fact, their overproduction in the most common types of cancers,
combined with their accessibility at the cell surface, makes the carcinoembryonic
antigens ideal targets for immunotherapy and gene therapy strategies.
I am indebted to the staff at Harwood Academic Publishers, who made this
enterprise possible, to the volume editors, each one an authority in his/her field, and
last but not least to the many competent contributors.
Christo Goridis
INTRODUCTION
It is perhaps unfortunate that human carcinoembryonic antigen (CEA) first came to
biomedical fame as a tumor-specific antigen and tumor marker. Its label as ‘tumor
specific’ was debunked when CEA was discovered in normal adult tissues, leading to
considerable disillusionment, and its denomination as a ‘tumor marker’ left it in the
category of a featureless label. The net effect was to divert attention away from CEA,
an unfortunate outcome when it is realized that CEA or CEA family members are
over-expressed or sometimes under-expressed in a high proportion of tumors at
virtually every site, particularly the major ones, such as colon, breast, lung and cervix.
In fact, CEA family changes may be the closest approximation of the holy grail of
cancer research: the much sought-after common molecular alteration.
It was the cloning of CEA family genes in 1986 that lead to a rebirth of basic and
applied interest in this family, resulting in an explosion of information, including the
precise molecular description of the family, the basis for the control of its expression
and important insights into its function. We have endeavored to capture the salient
features of this exciting phase of discovery in the pages of this book. Hopefully this will
help to advertise our realization that the CEA family is a ‘big player’ in human
cancer.
Already the new information is proving invaluable in more sophisticated useful
medical applications. The cell surface localization of CEA family glycoproteins has
made them an appealing target for the design of novel immunotherapeutic and
diagnostic modalities and this sphere of activity is reviewed in chapters by
Goldenberg et al., Hodge and Schlom, and Primus et al. The fact that CEA is
expressed in so many tumors has drawn attention to the use of the CEA
transcriptional promoter to drive toxic genes in gene therapy; a chapter by
Thompson deals with this interesting application.
On the fundamental research front, the CEA family appears to offer a possibly
unique window into evolution, as it represents a subset of the immunoglobulin gene
superfamily that is under relatively rapid change, possibly between that of repetitive
elements such as oligonucleotide repeats and that of common unique genes; in fact,
CEA itself seems to have appeared only recently in the primate radiation. This aspect