2nd International Conference on Tumor Microenvironment: Progression, Therapy and Prevention
Baden, Austria, June 25-29, 2002





The proper development and maintenance of most cellular systems requires the influence of specialized microenvironments. Hematopoiesis, for example, is dependent upon the microenvironment of the bone marrow. T cell differentiation requires thymic components and the microenvironment of mammary glands controls development and modeling of these glands. The concept that microenvironmental factors play an important role in cancer and in particular in metastasis formation exists for a long time. However, the dominant notion that changes in the DNA of oncogenes and tumor suppressor genes bear a major if not an exclusive responsibility not only for cancer development but also for its progression overshadowed, to a large extent, the area of tumor microenvironment.

This area was never dormant, however. An international workshop on "In Situ Tumor Immunity "dealing exclusively with cellular and humoral immunity in the tumor microenvironment was held in Tel Aviv in 1978. An international conference devoted to all aspects of "Tumor microenvironment" was held on the shore of the Sea of Galilee in Israel in 1995. This was a truly multidisciplinary event where the focal issue, the tumor microenvironment, was approached and discussed thoroughly by specialists from a wide spectrum of biomedical sciences.

The Baden conference (June 25-29, 2002) on "Tumor Microenvironment" met, in full, the intentions of the organizers to create a friendly forum that promotes a critical review of novel basic findings and of innovative clinical studies pertaining to the cancer microenvironment. An important portion of this highly successful scientific gathering is summarized in this volume.

It is my pleasure to acknowledge the superb work carried out by my colleagues in the organizing committee and to thank Ron Apte, Peter Czernilofsky, Smadar Fisher, Benjamin Sredni, Eitan Yefenof, Israel Vlodavsky and Dov Zipori for their devotion. I also express our gratitude to the sponsors of the conference and primarily to Boehringer Ingelheim Austria for very generous support.

Isaac P. Witz





The Molecular Basis of Metastasis

Progression, Therapy and Prevention of Raf Induced Lung Cancer in Mice
S. Storm, J. Fensterle and U.R. Rapp

PYST2, a MAPK Dual Specificity Phosphatase Is Regulated by Microenvironmental Factors
O. Levy-Nissenbaum, O. Sagi-Assif, S. Hantisteanu, P. Raanani, A. Avigdor, I. Ben-Bassat and I.P. Witz

Signaling and Control of Gene Expression

Gene Regulation in the Progression and Metastasis of Human Malignant Melanoma
E. McGary and M. Bar-Eli

Tumor – Microenvironment Interaction Modulates Gene Expression in Multiple Myeloma
S. Yaccoby, J. Shaughnessy, F. Zhan, B. Barlogie and J. Epstein

Overexpression of the Small Heat Shock Protein Hsp27 Affects the Metastatic Phenotype of Human Melanoma Cells In Vitro
S. Aldrian, F. Trautinger, I. Fröhlich, W. Berger, M. Micksche and I. Kindas-Mügge

Tumor-Stroma Interactions: Adhesion and Its Regulation

Regulation of Angiogenesis by the Extracellular Matrix and Protein Kinase A
J. Varner

Basement Membrane Defects in Xeno-Grafts of Malignant Human Cells
N. Mirancea, C. Schmidt, N. Daum, P. Tomakidi, H.-J. Stark, N.E. Fusenig and D. Breitkreutz

Control of Tumor Phenotype by Stromal Modulation
M.J. Willhauck, J.C. Mertens, A. Pavesio, N.E. Fusenig and H.J. Stark

Different Dynamics of Stromal Activation in Benign and Malignant Epithelial Tumors
S. Vosseler and N.E. Fusenig

Adhesion and Adhesion Molecules

Carbohydrate Recognition and Metastasis
Y. Takenaka, T. Fukumori and A. Raz

Cell Adhesion, Tumor Invasion, and Metastasis
U. Cavallaro, M. Herzig, J. Niedermeyer, M. Fuxa, B. Schaffhauser, I. Crnic, A.-K. Perl and G. Christofori

The Possible Role of Focal Adhesion Kinase (P125FAK) in the Malignancy of Human Melanoma
O. Kahana, M. Micksche, I.P. Witz and I. Yron

Adherence Up Regulates Expression of PYST2-L in Myeloid Leukemia Cells
S. Hantisteanu, O. Levy-Nissenbaum, O. Sagi-Assif, P. Raanani, A. Avigdor, I. Ben-Bassat and I.P. Witz

Cytokines in the Tumor Microenvironment

Stromal Cell-derived Factor 1 (SDF-1/CXCL12) in Malignant Glial Brain Tumors
M. De Rossi, M. Gelati, S. Frigerio, C. Calatozzolo, M. Eoli, B. Pollo, G. Broggi, E. Ciusani, A. Boiardi and A. Salmaggi

Mammary Adenocarcinoma Progression: Potential Role of Inter-relationships Between MCP-1, GM-CSF and TNF Alpha
E. Neumark, I.P. Witz and A. Ben-Baruch

IL-4 and IL 4d2 System in Host Defense Mechanism against Allergic and Tumor Diseases
R. Vasilenko, A. Vasiliev, I. Chikileva, A. Khodyakova, G. Puchkova, N. Kulikova, I. Kosarev, S. Andreev, L. Ptitsyn, V. Pavlov, V. Khlebnikov, V. Uversky, M. Kiselevsky and V. Abramov

Lytic Enzymes in the Tumor Microenvironment

Involvement of Heparanase in Cancer Metastasis, Angiogenesis and Normal Development
E. Zcharia, O. Goldshmidt, S. Metzger and I. Vlodavsky

Processing and Ectodomain Shedding of Membrane Type 1-Matrix Metalloproteinase and Regulation by Synthetic and Natural MMP Inhibitors
P. Osenkowski, M. Toth, M. Bernardo and R. Fridman

The Role of Protease Activated Receptor -1 (PAR-1) in Tumor Invasion and Metastasis, Angiogenesis, and Mammary Gland Morphogenesis
Z. Salah, Y.-J., Yin, M. Maoz, I. Cohen, B. Uziely, S. Grisaru-Granovsky and R. Bar-Shavit

Dissecting the Mechanism of Matrix Metalloproteinase-Induced Transformation of Mouse Mammary Epithelial Cells
D.C. Radisky, D.D. Levy and M.J. Bissell

Hypoxia Simultaneously Enhances Matrix Metalloproteinase 2 and Apoptosis in Endothelial Cells
Y. Ben-Yosef, S. Shapiro, A. Miller, and N. Lahat1

Predictive Value of Gelatinases in Urine and Analysis of Activation Mechanism of MMP-9 for Tumor Progression
M. Zuka, T. Tanaka and Y. Okada

Tumor Immunity and Immunotherapy

Monoclonal Antibodies in Cancer Therapy: Involvement of FcgR Expressed by Immune Effector Cells and by Tumor Cells
L. Cassard, W.H. Fridman and C. Sautès-Fridman

Unexpected High Frequency of Recombinant Antibodies Endowed with the Antigen-Specific, Major Histocompatibility Complex-Restricted Specificity of T Cells Isolated from a Large Naive Human Library
A. Lev, G. Denkberg, C.J. Cohen, H.R. Hoogenboom and Y. Reiter

Directing Cytotoxic T-cells to Tumor Cells by Antibody-mediated Targeting of Single-chain Class I MHC-peptide Complexes
A. Lev, D. Segal and Y. Reiter

T Cell Memory and Immunotherapy in Breast Cancer
V. Schirrmacher

T Cell Memory to Cell-bound Antigen
Y.D. Mahnke and V. Schirrmacher

Growth Inhibition of Prostate Adenocarcinoma In Vitro and In Vivo by Anti Her2 Immunotoxins
R. Rabinovsky, E. Zeira, E. Galun, J.W. Uhr, E. Vitteta and E. Yefenof

Anti-cancer Mucosal Vaccines: Therapeutic Efficacy Against Cancers Growing in Mucosal Organs
U. Qimron, N. Madar, E. Bar-Haim, L. Eisenbach, H.F. Staats and A. Porgador

Vaccine to Combat Immunosuppressive Stroma-derived Factor in Uterine Cervix Cancer
H. Le Buanec, B. Bizzini, A. Burny, R.C. Gallo and D. Zagury

Identification of Novel CD44 Ligands May Provide New Targets for Therapy
L. Melnik, M. Rochman, D. Ronen, Y. Zick, D. Naor and I. Golan

Novel Approaches for Cancer Therapy

The Synergistic Activity of AS101 and PMA on HL-60 Cells Differentiation: Mechanism of Action
M. Bouganim, Y. Kalechman, M. Albeck and B. Sredni

Induction of Apoptosis by the Immunomodulator AS101 in Ha-Ras Transformed Cells
S. Eliyahu, S. Dovrat, M. Albeck, S. Segal and B. Sredni

Studies of Specific Activity of Human Recombinant Lymphotoxin with the Use of Transplantable Lymphosarcoma Lio-1 Cell Line
A.A. Denisov, L.V. Mikhina, O.A. Karpova, Y.S. Dorovatovskaya, A.V. Tretyakova, S.V. Mel’nikova, R.V. Borovick and N.R. Dyadishchev

Prospects of Recombinant Human Prothymosin a in Antitumor Immunotherapy
A. Khodyakova, L. Khromykh, R. Vasilenko, A. Vasiliev, I. Brisgalov, G. Puchkova, G. Kozlovskaya, I. Kosarev, V. Khlebnikov, V. Uversky, M. Kiselevsky and V. Abramov


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