By W. C. Powell, L. M. Matrisian (auth.), Ursula Günthert Ph.D., P.D., Professor Walter Birchmeier Ph.D. (eds.)
In metastasis, tumor cells disseminate from the first lesion and residential to secondary organs the place they could stay dormant for a very long time. Metastasis formation continues to be the main feared manifestation for tumor sufferers and clinicians. even though advancements were made referring to previous detection and particular remedy, many of the melanoma sufferers nonetheless die of far away metastases. The pu-rpose of those 3 volumes is to check the new growth in molecular metas tasis examine and to try to additional comprehend the biol ogy of this multifocal technique. With admire to offer day molecular biology, the pioneers of metastasis learn tested the fundamental recommendations of metasta sis formation within the Nineteen Seventies and Eighties, particularly, clonal choice of metastatic cells, heterogeneity of metastatic subpopulations, organ specificity of metastasis and the significance of angio genesis (Fidler, Kripke, Nicolson, Folkman and others). within the Eighties and Nineties, numerous of the molecules concerned have been pointed out and their community interactions elucidated. those 3 volumes of present themes in Microbiology and Immuno logy bring together the latest advancements on those meta stasis-related molecules; their interactions, legislation, and how one can intrude with their motion. It turned obvious that metastasis-related molecules are limited to distinctive mobile cubicles, resembling the extracellular house, the mobilephone membrane, the cytoplasmic signalling community, and the nuclear regulatory procedure. For the advanced metastatic cascade, proteolysis and changes in adhesive services are the obvious and hence probably the most completely investigated processes.
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Additional info for Attempts to Understand Metastasis Formation I: Metastasis-Related Molecules
Biochem J 304: 263-269 Welgus HG, Fliszar CJ, Seltzer JL, Schmid TM, Jeffrey JJ (1990) Differential susceptibility of type X collagen to cleavage by two mammalian interstitial collagenases and 72-kDa type IV collagenase. J Bioi Chem 265: 13521-13527 Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI (1989) SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages [published erratum appears in J Bioi Chem 1990 Dec 25; 265(36): 225701.
Nature 370: 61-B5 Seltzer JL, Lee AY, Akers KT, Sudbeck B, Southon EA, Wayner EA, Eisen AZ (1994) Activation of 72-kDa type IV collagenase/gelatinase by normal fibroblasts in collagen lattices is mediated by integrin receptors but is not related to lattice contraction. Exp Cell Res 213: 356-374 Stetler SW, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Bioi 9: 541-573 Strongin AY, Marmer BL, Grant GA, Goldberg GI (1993) Plasma membrane-dependent activation of the 72-kDa type IV collagenase is prevented by complex formation with TIMP-2.
For example, MMP-3 activates proMMP-1 Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, Japan 24 M. Seiki and proMMP-9 (HE et al. 1989; SUZUKI et al. 1990). Thus, the serine proteases are expected to be the initiator for a complex array of activation cascades of proMMPs in tissue. Activation of proMMP-2, which degrades type IV collagen in the basement membrane and therefore is believed to play an essential role in tumor invasion and ultimately in metastasis (LlonA et al.