Osteopontin: Possible role in prostate cancer progression

Human prostate cancer has the propensity to metastasize to the bone where r eciprocal cellular interactions between prostate cancer and bone cells are known to occur. Osteopontin (OPN), a noncollagenous bone extracellular matr ix, is a secreted adhesive glycoprotein with a functional RGD cell-binding domain that interacts with the alpha(v)beta(3) cell surface integrin hetero dimer. OPN has been associated with malignant transformation as well as bei ng ligand to the CD44 receptor. Polyclonal antibodies to human OPN (hOPN) w ere prepared, and specificity was shown by pre-absorption with recombinant hOPN. The stimulatory effect of hOPN protein and the inhibitory effect of h OPN antibody on human prostate cancer cell lines LNCaP and C4-2 were assess ed by induction or inhibition of anchorage-independent growth, respectively . Expression of hOPN mRNA in prostate cancer cell lines and human prostate cancer tissue specimens were measured by mRNA blot analysis. Protein expres sion was assessed by immunohistochemistry in human prostate cancer specimen s and by Western blot analysis in prostate cancer cell lines. hOPN stimulat ed anchorage-independent growth of the human prostate cancer cell lines LNC aP and C4-2 in vitro. Antibodies to hOPN inhibited the growth-stimulatory e ffect by endogenous OPN, which can be overcome by the addition of exogenous hOPN, hOPN mRNA and protein are expressed in human prostate cancer cell li nes in vitro and in clinical human prostate cancer specimens, These finding s taken together suggest that OPN may act as a paracrine and autocrine medi ator of prostate cancer growth and progression.