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Effects of the bone morphogenetic protein binding protein spp24 (secreted phosphoprotein 24 kD) on the growth of human lung cancer cells
Author(s) -
Lee KwangBok,
Murray Samuel S.,
Duarte M. Eugenia L.,
Spitz Juliana F.,
Johnson Jared S.,
Song KyungJin,
Brochmann Elsa J.,
Taghavi Cyrus E.,
Keorochana Gun,
Liao JenChung,
Wang Jeffrey C.
Publication year - 2011
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21383
Subject(s) - autocrine signalling , bone morphogenetic protein , cancer research , phosphoprotein , bone morphogenetic protein 7 , bone morphogenetic protein 2 , growth factor , cell growth , microbiology and biotechnology , chemistry , biology , medicine , biochemistry , phosphorylation , receptor , in vitro , gene
Bone morphogenetic proteins (BMPs) and transforming growth factor‐beta (TGF‐β) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP‐2 and TGF‐β and to markedly inhibit the osteogenic properties of rhBMP‐2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP‐2) and reduce tumor growth in a system (A549 human non‐small cell lung cancer cell line) where autocrine stimulation by BMP‐2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co‐injection of BMP‐2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP‐2 and reduced the tumor growth when added to tumor cells that were not treated with BMP‐2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP‐2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1712–1718, 2011