The expression of Pim-1 and Endothelin-1 in osteolytic and osteoblastic metastatic carcinoma to bone

Certain tumors are known to induce an osteoblastic response when metastasizing to bone, but the exact mechanism by which the neoplastic cells stimulate new bone formation is only partially understood. The selective orthotropism in these neoplasms has been investigated and numerous factors have been implicated. Endothelin-1 is a potent peptide produced by endothelial cells. It is also produced by and affects bone cells and this is thought to play a role in osteoblastic metastasis. Independently, Pim-1, a serine/threonine protein kinase, is involved in the regulation of cell growth, differentiation, and apoptosis. The overexpression of this proto-oncogene is linked to the development of lymphoma, and recent studies have demonstrated that it also plays an important role outside of hematopoietic system. Recently, Roh et al ( Cancer Res 2003;63:8079-84) at our institution have demonstrated that overexpression of Pim-1 promotes genomic instability in prostate carcinoma, one of few types of carcinomas that are characteristically known to induce osteoblastic response when they metastasize. The exact role of Pim-1 in osteoblastic tumor metastasis and its expression in various tumor types have not been characterized. A search of our files returned 19 cases of metastatic carcinomas to bone with documented osteoblastic/osteolytic host response. We are currently investigating the expression of Pim-1 and endothelin-1 by immunohistochemical staining.