OSTEOPONTIN EXPRESSION AND DISTRIBUTION IN HUMAN CARCINOMAS

Osteopontin (OPN), a secreted adhesive glycoprotein, is significantly overexpressed in a variety of experimental models of malignancy. Moreo ver, increased levels of OPN have been detected in the blood of patien ts with metastatic carcinoma. To investigate OPN expression and distri bution in human carcinomas directly, we studied a wide variety of comm on tumors by Northern analysis, in situ hybridization, and immunohisto chemistry. All 14 tumors studied by Northern analysis showed very subs tantial increases in OPN messenger (m)RNA when compared to correspondi ng normal tissues. Moreover, intense labeling for OPN mRNA was detecte d in 71 of 76 carcinomas studied by in situ hybridization. In most of the carcinomas studied (colon, stomach, duodenum, pancreas, breast, lu ng, bladder, prostate, ovary, thyroid, and melanoma), tumor cells did not label detectably for OPN mRNA; however, macrophages intimately ass ociated with tumor cells labeled strongly for the OPN transcript. In c arcinomas of the kidney and endometrium, both tumor cells and host mac rophages labeled strongly for OPN mRNA. The presence of OPN mRNA in ma crophages was particularly pronounced at the edge of tumors (ie, tumor /stroma interface) and in areas of tumor necrosis. Although in most ca ses tumor cells did not label detectably for OPN mRNA, both tumor cell s and macrophages stained for OPN protein, suggesting that OPN mRNA, b oth tumor cells and macrophages stained for OPN protein, suggesting th at OPN secreted by macrophages may bind to tumor cells, possibly throu gh the glycine-arginine-glycine-aspartate-serine cell binding domain i n OPN. Collectively, these data suggest that OPN functions in adhesive interactions at the tumor/host interface and thereby may influence pr ocesses such as invasion and metastasis.