Attempts to Understand Metastasis Formation II: Regulatory by R. K. Singh, I. J. Fidler (auth.), Ursula Günthert Ph.D.,

By R. K. Singh, I. J. Fidler (auth.), Ursula Günthert Ph.D., PD, Professor Walter Birchmeier Ph.D. (eds.)

In the final decade the molecular biology of tumor versions has published the id of numerous metastasis- similar molecules. those volumes try to evaluate the latest ways in their mechanisms, rules and technique to deal with their malignant adjustments. the 1st quantity covers the presentation of proteases and inhibitors and their position in invasion of tumor cells, additionally mobile adhesion molecules and their interplay with the extracellular matrix. within the moment quantity the law of tumor development and angiogenesis via cytokines, development components and motility elements is printed. The 3rd quantity offers with detection of micrometastases and healing techniques, comparable to immunotherapy, gene remedy, chemotherapy and surgical thoughts to strive against metastatic unfold.

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The role of a4~1 and a4~7 in leukocyte pathophysiology has been recently reviewed (LoBB and Hemcer 1994). For those tumor cells that expressed ~1-integrins, antibodies to a4~1-integrin subunits inhibited their adhesion to endothelium substrates (TAICHMAN et al. 1991; 22 R. Giavazzi KAWAGUCHI et al. 1992; MATTILA et al. 1992; MARTIN-PADURA et al. 1991). However, other ~l-integrins, such as a5~1-integrin, have been shown to be involved in the adhesion of different tumor types, including melanoma and osteosarcoma, to cytokine-treated endothelial cells (LAuRI et al.

J Bioi Chern 268: 22883-22894 Tomita V, Saito T, Saito K, Oite T, Shimizu F, Sato S (1995) Possible significance of VLA-4 (a. ~,) for hematogenous metastasis of renal-cell cancer. Int J Cancer 60: 753-758 Tozeren A, Kleinman HK, Grant DS, Morales D, Mercurio AM, Byers SW (1995) E-selectin-rnediated dynamic interactions of breast- and colon-cancer cells with endothelial-cell monolayers. Int J Cancer 60: 426-431 30 R. Giavazzi: Cytokine-Mediated Tumor-Endothelial Cell Interaction in Metastasis Tsujisaki M, Imai K, Hirata H, Hanzawa Y, Masuya J, Nakano T, Sugiyama T, Matsui M, Hinoda Y, Yachi A (1991) Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases.

1990; KAGHESHITA et al. 1993), and a soluble form of ICAM-1 has been· found to be elevated in the serum of patients with malignant disease (GIAVAZZI et al. 1994; HARNING et al. 1991; TSUJISAKI et al. 1991; BANKS et al. 1993). The expression and shedding of ICAM-1 can be induced by inflammatory cytokines and is therefore of critical importance for ICAM-1mediated immunosurveillance (WEBB et al. 1991; NAGANUMA et al. 1991; ANICHINI et al. 1990). By analogy to these findings, the immunoglobulin family adhesion molecule PECAM-1, which is normally expressed on endothelial cells, has been found to be constitutively expressed on solid tumors and involved in nonstimulated tumor-endothelial cell interaction (TANG et al.

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