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. Author manuscript; available in PMC: 2011 Dec 1.
Published in final edited form as: Semin Cell Dev Biol. 2010 Sep 9;21(9):951–960. doi: 10.1016/j.semcdb.2010.08.009

Figure 3. EGFR may play multiple roles in breast cancer-induced osteolysis.

Figure 3

(A) In normal bone RANKL stimulation of osteoclast-mediated bone turnover and is balanced by the OPG antagonist of RANKL. (B) An EGFR ligand (light blue hexagon) expressed and shed by tumor cells may stimulate paracrine signaling by EGFR (double black bars) expressed by osteoblasts. This would inhibit OPG expression by osteoblasts, leading to increased RANKL stimulation of RANK expressed by osteoclasts and increased osteoclast-mediated bone turnover. (C) An EGFR ligand expressed and shed by tumor cells may stimulate autocrine signaling by EGFR expressed by the tumor cells, leading to PTHrP expression by these tumor cells. This stimulates RANKL expression and inhibits OPG expression by osteoblasts, again leading to increased RANKL stimulation of RANK expressed by osteoclasts and increased osteoclast-mediated bone turnover. (D) PTHrP expressed by tumor cells can also stimulate expression of an EGFR ligand by osteoblasts, leading to autocrine EGFR signaling and coupling to increased RANKL expression and decreased OPG expression in osteoblasts. Again, this leads to increased RANKL stimulation of RANK expressed by osteoclasts and increased osteoclast-mediated bone turnover.