title: Effects of the bone morphogenetic protein binding protein spp24 (secreted phosphoprotein 24 kD) on the growth of human lung cancer cells.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, University of California, UCLA Comprehensive Spine Center, 1250 16th Street 7th Floor Tower, No. 745, Los Angeles, California 90095-7036, USA.
authors.forename: Kwang-Bok
authors.initials: KB
authors.lastname: Lee
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Murray
authors.forename: M Eugenia L
authors.initials: ME
authors.lastname: Duarte
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Spitz
authors.forename: Jared S
authors.initials: JS
authors.lastname: Johnson
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Song
authors.forename: Elsa J
authors.initials: EJ
authors.lastname: Brochmann
authors.forename: Cyrus E
authors.initials: CE
authors.lastname: Taghavi
authors.forename: Gun
authors.initials: G
authors.lastname: Keorochana
authors.forename: Jen-Chung
authors.initials: JC
authors.lastname: Liao
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015891:Cystatins / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010750:Phosphoproteins / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D015891:Cystatins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C091340:secreted phosphoprotein 24