MetaMol's commitment to the development of anti-metastasis drugs is derived from studies of osteopontin, a glycoprotein that is normally secreted by cells of the immune system. Osteopontin has also been associated with metastasis formation by various cancers. Because the immune system can suppress tumor growth it was implied that there needed to be differences between host osteopontin and tumor-derived osteopontin that account for their distinct functions. Because we had previously identified aberrant processing of RNA (splicing) as a mechanism of deregulation of metastasis genes in cancer, we investigated osteopontin splicing in breast cancer cells. We discovered that the shortest splice form “osteopontin-C” is exclusively present in 75-80% of breast cancers, while not even a trace is detectable in normal breasts. Further, osteopontin-C plays an important role in conveying aggressive behavior to breast cancer cells as it strongly supports anchorage-independence. Without anchorage-independence, disseminating cancer cells could not survive in the circulation.
These observations have defined osteopontin-C as a useful diagnostic tool for determining the aggressiveness of cancers and as a potential drug target. MetaMol is also developing inhibitors of osteopontin-C. This is significant because the inhibition of a functionally important molecule that is present on about ¾ of all breast cancers will provide treatment options to the majority of patients who currently succumb.