MOUSE MAMMARY-CARCINOMA CELL-LINE (BALB C-MC) STIMULATES OSTEOCLAST FORMATION FROM MOUSE BONE-MARROW CELLS THROUGH CELL-TO-CELL CONTACT/

We recently reported that numerous osteoclasts (OC) were formed in coc ultures of some mouse cancer cell lines and bone marrow cells. In this study, we examined mechanisms by which one of the cell lines, BALB/c- MC, induces OC, BALB/c-MC dose dependently stimulated OC formation in cocultures, In cocultures where direct cell-to-fell contact between BA LB/c-MC and bone marrow cells was inhibited by membrane biters, OC for mation was not stimulated. The stimulation of OC formation in the cocu lture was completely abolished by adding 10(-7)-10(-6) mol/L indometha cin.,The concentration of prostaglandin E-2 (PGE(2)) in the culture me dia of cocultures with cell-to-cell contact was higher than that of co cultures without cell-to-cell contact or marrow cultures alone, and it reached levels sufficient to induce OC (11.9 +/- 5.3 ng/mL [about 3.4 x 10(-8) mol/L]), When BALB/ c-MC or bone marrow cells were fixed wit h formalin and then cocultured with bone marrow cells or BALB/c-MC, re spectively, the concentration of PGE, in the culture media of cocultur es of fixed BALB/c-MC and bone marrow cells increased, whereas that of cocultures of BALB/c-MC and fixed bone marrow cells did not increase. These results indicate that BALB/c-MC stimulate OC formation through direct cell-to-cell contact,vith bone marrow cells, and PGE, released from bone marrow cells through direct cell-to-cell contact are involve d in OC formation by the cell line. (Bone 23:27-32; 1998) (C) 1998 by Elsevier Science Inc. All rights reserved.