Calcium signals in prostate cancer cells: specific activation by bone-matrix proteins

Cancer of the prostate commonly metastasizes to bony sites where cells acqu ire an aggressive, rapidly proliferating, androgen-independent phenotype. T he interaction between bone and prostate, thus, becomes a key factor in dis ease progression. Fluctuations in intracellular ionized Ca2+ [Ca2+], are ra pid, regulated signal transduction events often associated with cell prolif eration. Hence, Ca2+ signals provide a convenient measure of early events i n cancer cell growth. This study developed single cell fluorescent imaging techniques to visualize Ca2+ signals in Fura-2 loaded prostatic cancer cell lines of various metastatic phenotypes. Solubilized bone fractions contain ing extracellular matrix and associated proteins were tested for the abilit y to trigger Ca2+ signals in prostate cancer cell lines. Fractions represen ting the complete repertoire of non-collagenous proteins present in mineral ized bone were tested. Results demonstrated that two bone fractions termed D3b- and D4a-triggered Ca2+ signals in prostate cancer cells derived from b one (PC-3), but not brain (DU-145) metastases of prostate cancer. Lymph-nod e derived LNCaP cells also did not produce a Ca2+ signal in response to add ition of soluble bone matrix. No other bone fractions produced a Ca2+' sign al in PC-3 cells. It is of interest that bone fractions D3b and D4a contain a number of non-collagenous matrix proteins including osteonectin (SPARC) and osteopontin (OPN), as well as prothrombin. Moreover, antibody LM609 tha t recognizes the alpha(v)beta(3) integrin, blocks the ability of OPN to tri gger a Ca2+ transient in PC-3 cells. These studies support a conclusion tha t bone-matrix proteins play a role in the growth and progression of metasta tic prostate cancer, and that prior growth in bone may be associated with d evelopment of a bone-matrix-responsive phenotype, (C) Harcourt Publishers L td 2000.