Between 1970 and 1994, cancer claimed the lives of about 0.5 million Americans every year. According to the most recent statistics, it is estimated that approximately 1.3 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. Despite these statistics, the prognosis of some cancers is excellent. Melanoma offers one good example. If diagnosis is made before the cancer has spread from its site of origin, cure is commonly achieved. Likewise, breast and prostate cancers have 5-year survival rates in excess of 80%. As with most cancers however, melanomas as well as breast and prostate cancers that have spread to distant organs, are rarely curable. The development of therapeutic strategies for the prevention and treatment of metastatic cancers thus represents a key priority for the pharmaceutical industry (see "Cancer Treatment 2002" a full analysis of current and future pharmaceutical approaches to cancer). Protein tyrosine phosphatases (PTPases), such as SHP-1 and SHP-2, that contain Src homology 2 (SH2) domains play important roles in growth factor and cytokine signal transduction pathways. In 1996, a protein of approximately 115 to 120 kDa that interacts with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts and termed SHPS-1 (SHP substrate 1). Various mitogens, including serum, insulin, and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2 in cultured cells. Increasing evidence has shown that SHPS-1 is involved in various biological phenomena, including suppression of anchorage-independent cell growth, negative regulation of immune cells, self-recognition of red blood cells, mediation of macrophage multinucleation, skeletal muscle differentiation, entrainment of circadian clock, neuronal survival and synaptogenesis. The expression of SHPS-1 is down-regulated by several oncogene products such as v-Src in fibroblasts. In addition, the down-regulation of SHPS-1 is also found in human breast cancer tissues compared with the matched normal tissues. On the other hand, forced expression of SHPS-1 suppresses anchorage-independent cell growth of v-Src-transformed cells in vitro as well as peritoneal dissemination of the cells in nude mice. The extracellular region of SHPS-1, which interacts with fibronectin, seems to take part in the inhibitory effect. This growing area of research thus offers considerable opportunities for the development of therapeutic strategies that may be able to limit tumor dissemination.

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