Proteases in the schistosome life cycle: a paradigm for tumour metastasis

Abstract

Cancers and parasites have a number of properties in common, particularly those that relate to their respective capacities to evade host defence mechanisms. This review highlights the similarities between metastatic tumours and schistosomes in particular, and describes the role that proteases may have in the migration, growth, survival and transmission of the different stages of the schistosome life-cycle in the vertebrate host. An elastase-like serine protease of schistosome larvae has been particularly well characterized, and its substrate profile and other properties are indicative of a role in facilitating migration of the parasite through skin tissue early after infection. The primary structures of a cathepsin B-like enzyme, and a putative 'haemoglobinase' found in adult worms have also recently been derived, these enzymes being responsible for degradation of haemoglobin in erythrocytes upon which the adults feed. Adult schistosome worms reside and produce eggs intravascularly, and the processes that mediate the extravasation and subsequent migration of the egg through host tissue are dependent on both blood platelets and the immune response. Fibrino(geno)lytic enzymatic activity that is present in the egg could modulate the thrombogenic potential that eggs might have as a result of their capacity to cause platelet aggregation in vitro and in vivo. The roles of other proteases and peptidases that have been found in schistosome larvae, worms and eggs are less clear. Some of these enzymes may modulate immunological and haemostatic defence mechanisms and thus prolong survival of the parasite, and the consequences of the interactions between schistosomes and host protease inhibitors could also be immune modulatory.

T Cell–Derived IL-4/IL-13 Protects Mice against Fatal Schistosoma mansoni Infection Independently of Basophils

“…mansoni eggs produce numerous tissue-destructive enzymes and toxic compounds (7)(8)(9). To prevent excessive tissue damage, the eggs are shielded off by formation of granulomas that are mainly composed of eosinophils, macrophages, and T cells, among which, CD4 + T cells were shown to play an important role for granuloma formation (10)(11)(12)(13).…”

Cleavage of Human IgE Mediated by <i>Schistosoma mansoni</i>

“…high or low pH, or the presence or absence of reducing agents. The ability of S. mansoni extracts to cleave IgG is, in fact, a controversial issue, with some groups reporting the existence of proteases which cleave rabbit and goat IgG [21]and human IgG [22], and suggesting that IgG-derived peptides may modulate the cytotoxic activities of macrophages in rats and humans [23, 24, 25]. However, others find proteases secreted by freshly transformed schistosomula do not cleave human IgG [26].…”

Introductionary overview

“…As supported by work reviewed in this volume [4][5][6][7][8][9][10], a general aspect of malignant neoplasms may be an imbalance of proteolysis which favors invasion. However, it is important to emphasize that proteolysis of tissue barriers is not a property unique to tumor cells.…”

“…Proteolysis is also a necessary component of angiogenesis by normal endothelial cells [6]. Non-neoplastic pathologic invasion by parasites [5] and bacterial agents, embryo morphogenesis, and wound healing all require proteolysis of extracellular matrix barriers.…”

“…This is because cell migration during invasion requires attachment and deattachment of the cell as it moves forward. This concept is just as true for trophoblasts [4] and shistosomes [5] as it is for tumor cells. Lysis of all matrix components around the invading cell would remove the substratum necessary for proper cell traction.…”