Attempts to Understand Metastasis Formation I: Metastasis-Related Molecules

301 Pages·1996·7.231 MB·English

by  W. C. Powell, L. M. Matrisian (auth.), Ursula Günthert Ph.D., P.D., Professor Walter Birchmeier Ph.D. (eds.)

Current Topics in
Microbiology
213/1 and Immunology
Editors
R.W. Com pans, Atlanta/Georgia
M. Cooper, Birmingham/Alabama· H. Koprowski,
Philadelphia/Pennsylvania· F. Melchers, Basel
M. Oldstone, La Jolla/California· S. Olsnes, Oslo
M. Potter, Bethesda/Maryland· H. Saedler, Cologne
P.K. Vogt, La Jolla/California· H. Wagner, Munich
Springer
Berlin
Heidelberg
New York
Barcelona
Budapest
Hong Kong
London
Milan
Paris
Santa Clara
Singapore
Tokyo
Attempts to Understand
Metastasis Formation I
Metastasis-Related Molecules
Edited by U. Gunthert and W. Birchmeier
With 35 Figures
Springer
URSULA GONTHERT, Ph.D., P.O.
Basel Institute for Immunology
GrenzacherstraBe 487
CH-4005 Basel
Switzerland
Professor WALTER BIRCHMEIER, Ph.D.
Max-DelbrOck-Centrum fOr Molekulare Medizin
Robert-R6ssle-StraBe 10
0-13122 Berlin
Germany
Cover illustration: Tumor cells, like lymphocytes, interact
with their surface receptors with corresponding receptors on
endothelial cells during intra- and extravasation. Metasta
sizing tumor cells extravasate from the blood or lymphatic
vessels through the endothelial lining into the extracellular
matrix of the underlying tissue. The requirement of specific
cell surface structures and of secreted proteolytic enzymes
for this process, as depicted on the cover, is described in the
chapters of this volume.
Cover design: KDnkel+Lopka, IIvesheim
ISSN 0070-217X
ISBN-13: 978-3-642-64697-3 e-ISBN-13: 978-3-642-61107-0
001: 10.1007/978-3-642-61107-0
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© Springer-Verlag Berlin Heidelberg 1996
Softcover reprint of the hardcover 1st edition 1996
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Preface
In metastasis, tumor cells disseminate from the primary
lesion and home to secondary organs where they may remain
dormant for a long time. Metastasis formation is still the most
feared manifestation for tumor patients and clinicians.
Although improvements have been made concerning earlier
detection and specific therapy, most of the cancer patients
still die of distant metastases. The pu-rpose of these three
volumes is to review the recent progress in molecular metas
tasis research and to attempt to further understand the biol
ogy of this multifocal process.
With respect to present day molecular biology, the pioneers of
metastasis research established the basic concepts of metasta
sis formation in the 1970s and 1980s, namely, clonal selection of
metastatic cells, heterogeneity of metastatic subpopulations,
organ specificity of metastasis and the importance of angio
genesis (Fidler, Kripke, Nicolson, Folkman and others). In the
1980s and 1990s, several of the molecules involved were
identified and their network interactions elucidated. These
three volumes of Current Topics in Microbiology and Immuno
logy compile the most recent developments on these meta
stasis-related molecules; their interactions, regulation, and
ways to interfere with their action. It became evident that
metastasis-related molecules are confined to distinct cellular
compartments, such as the extracellular space, the cell
membrane, the cytoplasmic signalling network, and the nuclear
regulatory system.
For the complex metastatic cascade, proteolysis and
alterations in adhesive functions are the most obvious and
thus one of the most thoroughly investigated processes.
Various proteases and precursors (metalloproteinases and
serine proteases) and their inhibitors (tissue inhibitors of
metalloproteases, plasminogen activator inhibitors and serpins)
exhibit a sensitive complex of interplay - we are particularly
fascinated by their highly regulated nature. Not only the
proteases and their inhibitors are important in all the different
VI Preface
stages of metastasis formation, but also to the same extent
adhesive and "de-adhesive" interactions: metastatic cells
must constantly detach themselves from their old partners
and reattach to new ones, as mainly outlined in the first
volume and partly in the second volume. Among the wide
spread members of the adhesion molecule families, certain
immunoglobulins, integrins, cadherins, selectins, and hyaluro
nic acid receptors as well as their ligands are implicated in the
spread of metastatic cells. The control of the metastatic
cascade by these extracellularly acting molecules is
delicately balanced, and slight changes could affect the
establishment of the normal cellular organization and conse
quently promote metastasis formation. Strikingly, some
genes of adhesion molecules have recently been identified as
tumor suppressor genes in model organisms (e.g. Drosophila)
and are in fact mutated in metastasizing human tumors.
Growth of primary tumors and metastases is strictly-depen
dent on angiogenesis, the formation of new blood vessels. How
this process is regulated by cytokines is another topic of the
second volume. Cytokines are not only important in angio
genesis but are essential for the direct migration of metastatic
cells. Cytokines act through specific receptors which mediate
signals by different means, e.g., tyrosine phosphorylation. A
recent discovery is that cytoplasmic signal transduction
components, transcription factors, and cell cycle regulators
are also metastasis-related. Many of the presently described
genes in metastasis were known as activated oncogenes for
several years, but apparently the encoded gene products have
a broader spectrum of action than was originally assumed.
We have recently learned that the spread of metastatic
cells, especially of micrometastases, is far more extensive
than previously expected. A successful anti metastatic therapy
therefore requires new strategies: for this reason the third
volume comprises novel approaches such as immuno
therapy, transfer of tumor-inhibiting genes and anti-sense
constructs, as well as interference with signal transduction
pathways. Promising new therapeutic approaches also
involve the use of anti-angiogenic factors or of recombinant
soluble metastasis-related molecules which interfere with
ligand interactions.
As the process of metastatic spread is presently regarded
as a-multifactor event which is yet to be sufficiently understood
in the multitude of its aspects, approaches to clinical treatment
have to be polypragmatic. Methods of treatment are based on
chemotherapy and radiotherapy, refined and adapted to the
Preface VII
type of tumor pertaining and the pattern of metastatic spread.
Increasingly, therapies which incorporate new insights from
immunology and molecular biology are adopted for clinical
use. To present a rounded scope of the topic, these current
strategies are covered by the third volume in particular.
Surgical treatment options are indicated in cases where a
curative intervention is feasible e.g. in solitary metastases of
colorectal carcinoma, soft tissue, and kidney tumors.
We hope that the reader of these volumes is impressed
by the quality of the contents. Metastasis has obviously
emerged as a serious discipline of natural sciences due to the
fact that the molecular biology of various metastasis-related
molecules and their complex interplay became transparent.
We are, nevertheless, still in the beginning phase and await
further progress from which patients will finally benefit.
Most, if not all of the metastasis-specific processes des
cribed are also known to be involved in emorYonic development
and pattern formation, as well as in leukocyte biology. The
disciplines of metastasis research, developmental biology,
and immunology can, therefore, profit from and stimulate
each other. The genetic analysis of candidate molecules and
their interplays in transgenic mice will certainly further broaden
our understanding of the molecular basis of metastasis
formation.
We would like to thank the authors who have spent their
valuable time in writing a chapter for this series. Without their
expertise and cooperation, this compilation of newest
developments in metastasis research would not have been
attainable. Leslie Nicklin (Basel) assisted the edition of this
series with her competent skills; we are most grateful for her
contribution.
Basel URSULA GONTHERT
Berlin WALTER BIRCHMEIER
Berlin PETER M.SCHLAG
List of Contents
W.C. POWELL and L.M. MATRISIAN
Complex Roles of Matrix Metalloproteinases
in Tumor Progression ......................... .
M. SEIKI
Membrane Type-Matrix Metalloproteinase
and Tumor .Invasion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
P. MiGNATII and D.B. RIFKIN
Plasminogen Activators and Angiogenesis. . . . . . . . . . 33
R. SAGER, S. SHENG, P. PEMBERTON, and M.J.C. HENDRIX
Maspin: A Tumor Supressing Serpin . . . . . . . . . . . . . . . 51
B.M. MUELLER
Different Roles for Plasminogen Activators
and Metalloproteinases in Melanoma Metastasis. . . . . 65
M.J. REED and E.H. SAGE
SPARC and the Extracellular Matrix:
Implications for Cancer and Wound Repair. . . . . . . . . . 81
J.P. JOHNSON, M.M. RUMMEL, U. ROTHBACHER,
and C. SERS
MUC18: A Cell Adhesion Molecule
with a Potential Role in Tumor Growth
and Tumor Cell Dissemination. . . . . . . . . . . . . . . . . . . 95
R.C. ELBLE and B.U. PAULI
Lu-ECAM-1 and DPP IV in Lung Metastasis . . . . . . . . . 107
M.E. BRACKE, F.M. VAN Roy, and M.M. MAREEL
The E-cadherin/Catenin Complex in Invasion
and Metastasis............................... 123
S. BRAUN and K. PANTEL
Biological Characteristics
of Micrometastatic Carcinoma Cells
in Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
X List of Contents
B. BOYER, A.M. VALLES, and J.P. THIERY
Model Systems of Carcinoma Cell Dispersion. . . . . . 179
BA IMHOF, L. PIAU, R.H. GISLER, and D. DUNON
Involvement of a6 and av Integrins in Metastasis. . . 195
N. MONTUORI and M.E. SOBEL
The 67-kDa Laminin Receptor and Tumor Progression. 205
M. ZOLLER
Joint Features of Metastasis Formation
and Lymphocyte Maturation and Activation. . . . . . . . 215
L. SHERMAN, J. SLEEMAN, P. DALL, A. HEKELE, J. MOLL,
H. PONTA, and P. HERRUCH
The CD44 Proteins in Embryonic Development
and in Cancer ............................... 249
U. GONTHERT
CD44 in Malignant Diso·rders .................... 271
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
List of Contents
of Companion Volume 213/11
R.K. SINGH and I.J. FIDLER
Regulation of Tumor Angiogenesis
by Organ-Specific Cytokines
R. GIAVAZZI
Cytokine-Mediated Tumor-Endothelial Cell Interaction
in Metastasis
M.S. PEPPER, S.J. MANDRIOTA, J.-D. VASSALLI, L. ORCI,
and R. MONTESANO
Angiogenesis-Regulating Cytokines: Activities and Interactions
D.G. TANG and KV HONN
Adhesion Molecules and Tumor Cell-Vasculature Interactions:
Modulation by Bioactive Lipid Molecules
G.L. NICOLSON, D.G. MENTER, J.L. HERRMANN, Z. YUN,
P. CAVANAUGH, and D. MARCHEDI
Brain Metastasis: Role of Trophic, Autocrine,
and Paracrine Factors in Tumor Invasion and Colonization
of the Central Nervous System
W. BIRCHMEIER, J. BEHRENS, K.M. WEIDNER, J. HULSKEN,
and C. BIRCHMEIER
Epithelial Differentiation and the Control of Metastasis
in Carcinomas
S. SILLEDI and A. RAZ
Regulation of Autocrine Motility Factor
Receptor Expression in Tumor Cell Locomotion and Metastasis
E.M. LUKANIDIN and G.P. GEORGIEV
Metastasis-Related mts 1 Gene
R.J. MUSCHEL and W.G. McKENNA
Alterations in Cell Cycle Control During Tumor Progression:
Effects on Apoptosis and the Response
to Therapeutic Agents