Parathyroid hormone/parathyroid hormone-related peptide regulate osteosarcoma cell functions: Focus on the extracellular matrix (Review)

Nikitovic,Dragana; Kavasi,Rafaela‑Maria; Berdiaki,Aikaterini; Papachristou,Dionysios  J.; Tsiaoussis,John; Spandidos,Demetrios   A.; Tsatsakis,Aristides   M.; Tzanakakis,George  N.

doi:10.3892/or.2016.4986

Parathyroid hormone/parathyroid hormone-related peptide regulate osteosarcoma cell functions: Focus on the extracellular matrix (Review)

Authors:
- Dragana Nikitovic
- Rafaela‑Maria Kavasi
- Aikaterini Berdiaki
- Dionysios J. Papachristou
- John Tsiaoussis
- Demetrios A. Spandidos
- Aristides M. Tsatsakis
- George N. Tzanakakis
View Affiliations

Affiliations: Department of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, Heraklion 71003, Greece, Department of Anatomy‑Histology‑Embryology, Unit of Bone and Soft Tissue Studies, School of Medicine, University of Patras, Patras 26504, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71003, Greece, Laboratory of Toxicology, Medical School, University of Crete, Heraklion 71003, Greece
Published online on: August 1, 2016 https://doi.org/10.3892/or.2016.4986
Pages: 1787-1792
Copyright: © Nikitovic et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteosarcoma (OS) is a primary bone tumor of mesenchymal origin mostly affecting children and adolescents. The OS extracellular matrix (ECM) is extensively altered as compared to physiological bone tissue. Indeed, the main characteristic of the most common osteoblastic subtype of OS is non‑mineralized osteoid production. Parathyroid hormone (PTH) is a polypeptide hormone secreted by the chief cells of the parathyroid glands. The PTH-related peptide (PTHrP) may be comprised of 139, 141 or 173 amino acids and exhibits considerate N‑terminal amino acid sequence homology with PTH. The function of PTH/PTHrP is executed through the activation of the PTH receptor 1 (PTHR1) and respective downstream intracellular pathways which regulate skeletal development, bone turnover and mineral ion homeostasis. Both PTHR1 and its PTH/PTHrP ligands have been shown to be expressed in OS and to affect the functions of these tumor cells. This review aims to highlight the less well known aspects of PTH/PTHrP functions in the progression of OS by focusing on ECM-dependent signaling.

View Figures

View References

1	Mirabello L, Troisi RJ and Savage SA: International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 125:229–234. 2009. View Article : Google Scholar : PubMed/NCBI
2	Stiller CA, Bielack SS, Jundt G and Steliarova-Foucher E: Bone tumours in European children and adolescents, 1978–1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer. 42:2124–2135. 2006. View Article : Google Scholar : PubMed/NCBI
3	Fletcher CDM, Unni KK and Mertens F: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. IARC Press; Lyon: 2002
4	Ragland BD, Bell WC, Lopez RR and Siegal GP: Cytogenetics and molecular biology of osteosarcoma. Lab Invest. 82:365–373. 2002. View Article : Google Scholar : PubMed/NCBI
5	Bacci G, Longhi A, Fagioli F, Briccoli A, Versari M and Picci P: Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy. Eur J Cancer. 41:2836–2845. 2005. View Article : Google Scholar : PubMed/NCBI
6	Weiss A, Khoury JD, Hoffer FA, Wu J, Billups CA, Heck RK, Quintana J, Poe D, Rao BN and Daw NC: Telangiectatic osteosarcoma: The St. Jude Children's Research Hospital's experience. Cancer. 109:1627–1637. 2007. View Article : Google Scholar : PubMed/NCBI
7	Jaffe N, Carrasco H, Raymond K, Ayala A and Eftekhari F: Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery? Cancer. 95:2202–2210. 2002. View Article : Google Scholar : PubMed/NCBI
8	Mutsaers AJ and Walkley CR: Cells of origin in osteosarcoma: Mesenchymal stem cells or osteoblast committed cells? Bone. 62:56–63. 2014. View Article : Google Scholar : PubMed/NCBI
9	Lin PP, Pandey MK, Jin F, Raymond AK, Akiyama H and Lozano G: Targeted mutation of p53 and Rb in mesenchymal cells of the limb bud produces sarcomas in mice. Carcinogenesis. 30:1789–1795. 2009. View Article : Google Scholar : PubMed/NCBI
10	Mutsaers AJ, Ng AJ, Baker EK, Russell MR, Chalk AM, Wall M, Liddicoat BJ, Ho PW, Slavin JL, Goradia A, et al: Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA. Bone. 55:166–178. 2013. View Article : Google Scholar : PubMed/NCBI
11	Overholtzer M, Rao PH, Favis R, Lu XY, Elowitz MB, Barany F, Ladanyi M, Gorlick R and Levine AJ: The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc Natl Acad Sci USA. 100:11547–11552. 2003. View Article : Google Scholar : PubMed/NCBI
12	Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D, van Pel M, Cleton-Jansen AM and Hogendoorn PC: Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol. 219:294–305. 2009. View Article : Google Scholar : PubMed/NCBI
13	Vilardaga JP, Romero G, Friedman PA and Gardella TJ: Molecular basis of parathyroid hormone receptor signaling and trafficking: A family B GPCR paradigm. Cell Mol Life Sci. 68:1–13. 2011. View Article : Google Scholar
14	Huan J, Olgaard K, Nielsen LB and Lewin E: Parathyroid hormone 7–84 induces hypocalcemia and inhibits the parathyroid hormone 1–84 secretory response to hypocalcemia in rats with intact parathyroid glands. J Am Soc Nephrol. 17:1923–1930. 2006. View Article : Google Scholar : PubMed/NCBI
15	Cheloha RW, Gellman SH, Vilardaga JP and Gardella TJ: PTH receptor-1 signalling-mechanistic insights and therapeutic prospects. Nat Rev Endocrinol. 11:712–724. 2015. View Article : Google Scholar : PubMed/NCBI
16	Friedman PA and Goodman WG: PTH(1-84)/PTH(7-84): A balance of power. Am J Physiol Renal Physiol. 290:F975–F984. 2006. View Article : Google Scholar : PubMed/NCBI
17	Burton DW, Brandt DW and Deftos LJ: Parathyroid hormone-related protein in the cardiovascular system. Endocrinology. 135:253–261. 1994.PubMed/NCBI
18	Kronenberg HM: Developmental regulation of the growth plate. Nature. 423:332–336. 2003. View Article : Google Scholar : PubMed/NCBI
19	Abou-Samra AB, Jüppner H, Force T, Freeman MW, Kong XF, Schipani E, Urena P, Richards J, Bonventre JV and Potts JT Jr: Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: A single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. Proc Natl Acad Sci USA. 89:2732–2736. 1992. View Article : Google Scholar
20	Mannstadt M, Jüppner H and Gardella TJ: Receptors for PTH and PTHrP: Their biological importance and functional properties. Am J Physiol. 277:F665–F675. 1999.PubMed/NCBI
21	Kondo H, Guo J and Bringhurst FR: Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells. J Bone Miner Res. 17:1667–1679. 2002. View Article : Google Scholar : PubMed/NCBI
22	Cheung R, Erclik MS and Mitchell J: Increased expression of G11alpha in osteoblastic cells enhances parathyroid hormone activation of phospholipase C and AP-1 regulation of matrix metalloproteinase-13 mRNA. J Cell Physiol. 204:336–343. 2005. View Article : Google Scholar : PubMed/NCBI
23	Rey A, Manen D, Rizzoli R, Ferrari SL and Caverzasio J: Evidences for a role of p38 MAP kinase in the stimulation of alkaline phosphatase and matrix mineralization induced by parathyroid hormone in osteoblastic cells. Bone. 41:59–67. 2007. View Article : Google Scholar : PubMed/NCBI
24	Ferrari SL, Behar V, Chorev M, Rosenblatt M and Bisello A: Endocytosis of ligand-human parathyroid hormone receptor 1 complexes is protein kinase C-dependent and involves beta-arrestin2. Real-time monitoring by fluorescence microscopy. J Biol Chem. 274:29968–29975. 1999. View Article : Google Scholar : PubMed/NCBI
25	Vilardaga JP, Krasel C, Chauvin S, Bambino T, Lohse MJ and Nissenson RA: Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association. J Biol Chem. 277:8121–8129. 2002. View Article : Google Scholar
26	De Camilli P, Emr SD, McPherson PS and Novick P: Phosphoinositides as regulators in membrane traffic. Science. 271:1533–1539. 1996. View Article : Google Scholar : PubMed/NCBI
27	Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore MS, Linda Y and Nold JB: Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. Toxicol Pathol. 30:312–321. 2002. View Article : Google Scholar : PubMed/NCBI
28	Tashjian AH Jr and Gagel RF: Teriparatide [human PTH(1-34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis. J Bone Miner Res. 21:354–365. 2006. View Article : Google Scholar : PubMed/NCBI
29	Watanabe A, Yoneyama S, Nakajima M, Sato N, Takao-Kawabata R, Isogai Y, Sakurai-Tanikawa A, Higuchi K, Shimoi A, Yamatoya H, et al: Osteosarcoma in Sprague-Dawley rats after long-term treatment with teriparatide (human parathyroid hormone (1-34)). J Toxicol Sci. 37:617–629. 2012. View Article : Google Scholar : PubMed/NCBI
30	Subbiah V, Madsen VS, Raymond AK, Benjamin RS and Ludwig JA: Of mice and men: Divergent risks of teriparatide-induced osteosarcoma. Osteoporos Int. 21:1041–1045. 2010. View Article : Google Scholar
31	Harper KD, Krege JH, Marcus R and Mitlak BH: Comments on Initial experience with teriparatide in the United States. Curr Med Res Opin. 22:19272006. View Article : Google Scholar : PubMed/NCBI
32	Harper KD, Krege JH, Marcus R and Mitlak BH: Osteosarcoma and teriparatide? J Bone Miner Res. 22:3342007. View Article : Google Scholar
33	Andrews EB, Gilsenan AW, Midkiff K, Sherrill B, Wu Y, Mann BH and Masica D: The US postmarketing surveillance study of adult osteosarcoma and teriparatide: Study design and findings from the first 7 years. J Bone Miner Res. 27:2429–2437. 2012. View Article : Google Scholar : PubMed/NCBI
34	Ho PW, Goradia A, Russell MR, Chalk AM, Milley KM, Baker EK, Danks JA, Slavin JL, Walia M, Crimeen-Irwin B, et al: Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo. Oncogene. 34:2922–2933. 2015. View Article : Google Scholar
35	Yang D, Singh R, Divieti P, Guo J, Bouxsein ML and Bringhurst FR: Contributions of parathyroid hormone (PTH)/PTH-related peptide receptor signaling pathways to the anabolic effect of PTH on bone. Bone. 40:1453–1461. 2007. View Article : Google Scholar : PubMed/NCBI
36	Ardura JA, Wang B, Watkins SC, Vilardaga JP and Friedman PA: Dynamic Na+–H+ exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains. J Biol Chem. 286:35020–35029. 2011. View Article : Google Scholar : PubMed/NCBI
37	Kawane T, Mimura J, Yanagawa T, Fujii-Kuriyama Y and Horiuchi N: Parathyroid hormone (PTH) down-regulates PTH/PTH-related protein receptor gene expression in UMR-106 osteoblast-like cells via a 3′,5′-cyclic adenosine mono-phosphate-dependent, protein kinase A-independent pathway. J Endocrinol. 178:247–256. 2003. View Article : Google Scholar : PubMed/NCBI
38	Evans DB, Hipskind RA and Bilbe G: Analysis of signaling pathways used by parathyroid hormone to activate the c-fos gene in human SaOS2 osteoblast-like cells. J Bone Miner Res. 11:1066–1074. 1996. View Article : Google Scholar : PubMed/NCBI
39	Pearman AT, Chou WY, Bergman KD, Pulumati MR and Partridge NC: Parathyroid hormone induces c-fos promoter activity in osteoblastic cells through phosphorylated cAMP response element (CRE)-binding protein binding to the major CRE. J Biol Chem. 271:25715–25721. 1996. View Article : Google Scholar : PubMed/NCBI
40	Liao J and McCauley LK: Skeletal metastasis: Established and emerging roles of parathyroid hormone related protein (PTHrP). Cancer Metastasis Rev. 25:559–571. 2006. View Article : Google Scholar : PubMed/NCBI
41	Pasquini GM, Davey RA, Ho PW, Michelangeli VP, Grill V, Kaczmarczyk SJ and Zajac JD: Local secretion of parathyroid hormone-related protein by an osteoblastic osteosarcoma (UMR 106-01) cell line results in growth inhibition. Bone. 31:598–605. 2002. View Article : Google Scholar : PubMed/NCBI
42	García-Martín A, Acitores A, Maycas M, Villanueva-Peñacarrillo ML and Esbrit P: Src kinases mediate VEGFR2 transactivation by the osteostatin domain of PTHrP to modulate osteoblastic function. J Cell Biochem. 114:1404–1413. 2013. View Article : Google Scholar : PubMed/NCBI
43	Jemtland R, Rian E, Olstad OK, Haug E, Bruland OS, Bucht E and Gautvik KM: Two human osteoblast-like osteosarcoma cell lines show distinct expression and differential regulation of parathyroid hormone-related protein. J Bone Miner Res. 14:904–914. 1999. View Article : Google Scholar : PubMed/NCBI
44	Gagiannis S, Müller M, Uhlemann S, Koch A, Melino G, Krammer PH, Nawroth PP, Brune M and Schilling T: Parathyroid hormone-related protein confers chemoresistance by blocking apoptosis signaling via death receptors and mitochondria. Int J Cancer. 125:1551–1557. 2009. View Article : Google Scholar : PubMed/NCBI
45	Kresse H and Schönherr E: Proteoglycans of the extracellular matrix and growth control. J Cell Physiol. 189:266–274. 2001. View Article : Google Scholar : PubMed/NCBI
46	Afratis N, Gialeli C, Nikitovic D, Tsegenidis T, Karousou E, Theocharis AD, Pavão MS, Tzanakakis GN and Karamanos NK: Glycosaminoglycans: Key players in cancer cell biology and treatment. FEBS J. 279:1177–1197. 2012. View Article : Google Scholar : PubMed/NCBI
47	Sanderson RD, Yang Y, Suva LJ and Kelly T: Heparan sulfate proteoglycans and heparanase - partners in osteolytic tumor growth and metastasis. Matrix Biol. 23:341–352. 2004. View Article : Google Scholar : PubMed/NCBI
48	Maxwell CA, McCarthy J and Turley E: Cell-surface and mitotic-spindle RHAMM: Moonlighting or dual oncogenic functions? J Cell Sci. 121:925–932. 2008. View Article : Google Scholar : PubMed/NCBI
49	Xu R, Boudreau A and Bissell MJ: Tissue architecture and function: Dynamic reciprocity via extra- and intra-cellular matrices. Cancer Metastasis Rev. 28:167–176. 2009. View Article : Google Scholar : PubMed/NCBI
50	Kouvidi K, Nikitovic D, Berdiaki A and Tzanakakis GN: Hyaluronan/RHAMM interactions in mesenchymal tumor pathogenesis: Role of growth factors. Adv Cancer Res. 123:319–349. 2014. View Article : Google Scholar : PubMed/NCBI
51	Nikitovic D, Chalkiadaki G, Berdiaki A, Aggelidakis J, Katonis P, Karamanos NK and Tzanakakis GN: Lumican regulates osteosarcoma cell adhesion by modulating TGFβ2 activity. Int J Biochem Cell Biol. 43:928–935. 2011. View Article : Google Scholar : PubMed/NCBI
52	Unni KK: Osteosarcoma of bone. J Orthop Sci. 3:287–294. 1998. View Article : Google Scholar : PubMed/NCBI
53	Benayahu D, Shur I, Marom R, Meller I and Issakov J: Cellular and molecular properties associated with osteosarcoma cells. J Cell Biochem. 84:108–114. 2001. View Article : Google Scholar : PubMed/NCBI
54	Nikitovic D, Tsatsakis AM, Karamanos NK and Tzanakakis GN: The effects of genistein on the synthesis and distribution of glycosaminoglycans/proteoglycans by two osteosarcoma cell lines depends on tyrosine kinase and the estrogen receptor density. Anticancer Res. 23(1A): 459–464. 2003.PubMed/NCBI
55	Nikitovic D, Zafiropoulos A, Katonis P, Tsatsakis A, Theocharis AD, Karamanos NK and Tzanakakis GN: Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. IUBMB Life. 58:47–53. 2006. View Article : Google Scholar : PubMed/NCBI
56	Nikitovic D, Berdiaki K, Chalkiadaki G, Karamanos N and Tzanakakis G: The role of SLRP-proteoglycans in osteosarcoma pathogenesis. Connect Tissue Res. 49:235–238. 2008. View Article : Google Scholar : PubMed/NCBI
57	Nikitovic D, Aggelidakis J, Young MF, Iozzo RV, Karamanos NK and Tzanakakis GN: The biology of small leucine-rich proteoglycans in bone pathophysiology. J Biol Chem. 287:33926–33933. 2012. View Article : Google Scholar : PubMed/NCBI
58	Datta NS and Abou-Samra AB: PTH and PTHrP signaling in osteoblasts. Cell Signal. 21:1245–1254. 2009. View Article : Google Scholar : PubMed/NCBI
59	Sabbieti MG, Agas D, Xiao L, Marchetti L, Coffin JD, Doetschman T and Hurley MM: Endogenous FGF-2 is critically important in PTH anabolic effects on bone. J Cell Physiol. 219:143–151. 2009. View Article : Google Scholar :
60	Teplyuk NM, Haupt LM, Ling L, Dombrowski C, Mun FK, Nathan SS, Lian JB, Stein JL, Stein GS, Cool SM, et al: The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts. J Cell Biochem. 107:144–154. 2009. View Article : Google Scholar : PubMed/NCBI
61	Datsis GA, Berdiaki A, Nikitovic D, Mytilineou M, Katonis P, Karamanos NK and Tzanakakis GN: Parathyroid hormone affects the fibroblast growth factor-proteoglycan signaling axis to regulate osteosarcoma cell migration. FEBS J. 278:3782–3792. 2011. View Article : Google Scholar : PubMed/NCBI
62	Zafiropoulos A, Nikitovic D, Katonis P, Tsatsakis A, Karamanos NK and Tzanakakis GN: Decorin-induced growth inhibition is overcome through protracted expression and activation of epidermal growth factor receptors in osteosarcoma cells. Mol Cancer Res. 6:785–794. 2008. View Article : Google Scholar : PubMed/NCBI
63	Nikitovic D, Zafiropoulos A, Tzanakakis GN, Karamanos NK and Tsatsakis AM: Effects of glycosaminoglycans on cell proliferation of normal osteoblasts and human osteosarcoma cells depend on their type and fine chemical compositions. Anticancer Res. 25:2851–2856. 2005.PubMed/NCBI
64	El Khassawna T, Böcker W, Brodsky K, Weisweiler D, Govindarajan P, Kampschulte M, Thormann U, Henss A, Rohnke M and Bauer N: Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats. Histochem Cell Biol. 144:491–507. 2015. View Article : Google Scholar : PubMed/NCBI
65	Wang X, Harimoto K, Xie S, Cheng H, Liu J and Wang Z: Matrix protein biglycan induces osteoblast differentiation through extracellular signal-regulated kinase and Smad pathways. Biol Pharm Bull. 33:1891–1897. 2010. View Article : Google Scholar : PubMed/NCBI
66	Ruan K, Bao S and Ouyang G: The multifaceted role of periostin in tumorigenesis. Cell Mol Life Sci. 66:2219–2230. 2009. View Article : Google Scholar : PubMed/NCBI
67	Fortunati D, Reppe S, Fjeldheim AK, Nielsen M, Gautvik VT and Gautvik KM: Periostin is a collagen associated bone matrix protein regulated by parathyroid hormone. Matrix Biol. 29:594–601. 2010. View Article : Google Scholar : PubMed/NCBI
68	Nikitovic D, Kouvidi K, Kavasi RM, Berdiaki A and Tzanakakis GN: Hyaluronan/Hyaladherins - a Promising Axis for Targeted Drug Delivery in Cancer. Curr Drug Deliv. 13:500–511. 2016. View Article : Google Scholar
69	Midura RJ, Evanko SP and Hascall VC: Parathyroid hormone stimulates hyaluronan synthesis in an osteoblast-like cell line. J Biol Chem. 269:13200–13206. 1994.PubMed/NCBI
70	Midura RJ, Su X, Morcuende JA, Tammi M and Tammi R: Parathyroid hormone rapidly stimulates hyaluronan synthesis by periosteal osteoblasts in the tibial diaphysis of the growing rat. J Biol Chem. 278:51462–51468. 2003. View Article : Google Scholar : PubMed/NCBI
71	Berdiaki A, Datsis GA, Nikitovic D, Tsatsakis A, Katonis P, Karamanos NK and Tzanakakis GN: Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration. IUBMB Life. 62:377–386. 2010.PubMed/NCBI
72	Pacheco-Costa R, Campos JF, Katchburian E, de Medeiros VP, Nader HB, Nonaka KO, Plotkin LI and Reginato RD: Modifications in bone matrix of estrogen-deficient rats treated with intermittent PTH. BioMed Res Int. 2015:4541622015. View Article : Google Scholar : PubMed/NCBI
73	Kido A, Tsutsumi M, Iki K, Takahama M, Tsujiuchi T, Morishita T, Tamai S and Konishi Y: Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats. Cancer Lett. 137:209–216. 1999. View Article : Google Scholar : PubMed/NCBI
74	Wang J, Shi Q, Yuan TX, Song QL, Zhang Y, Wei Q, Zhou L, Luo J, Zuo G, Tang M, et al: Matrix metalloproteinase 9 (MMP-9) in osteosarcoma: Review and meta-analysis. Clin Chim Acta. 433:225–231. 2014. View Article : Google Scholar : PubMed/NCBI
75	Deryugina EI and Quigley JP: Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 25:9–34. 2006. View Article : Google Scholar : PubMed/NCBI
76	Husmann K, Arlt MJ, Muff R, Langsam B, Bertz J, Born W and Fuchs B: Matrix Metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model. Biochim Biophys Acta. 1832:347–354. 2013. View Article : Google Scholar
77	Egeblad M and Werb Z: New functions for the matrix metal-loproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI
78	Shuman Moss LA, Jensen-Taubman S and Stetler-Stevenson WG: Matrix metalloproteinases: Changing roles in tumor progression and metastasis. Am J Pathol. 181:1895–1899. 2012. View Article : Google Scholar : PubMed/NCBI
79	Uchibori M, Nishida Y, Nagasaka T, Yamada Y, Nakanishi K and Ishiguro N: Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma. Int J Oncol. 28:33–42. 2006.
80	Himelstein BP, Asada N, Carlton MR and Collins MH: Matrix metalloproteinase-9 (MMP-9) expression in childhood osseous osteosarcoma. Med Pediatr Oncol. 31:471–474. 1998. View Article : Google Scholar : PubMed/NCBI
81	Kimura R, Ishikawa C, Rokkaku T, Janknecht R and Mori N: Phosphorylated c-Jun and Fra-1 induce matrix metallopro-teinase-1 and thereby regulate invasion activity of 143B osteosarcoma cells. Biochim Biophys Acta. 1813:1543–1553. 2011. View Article : Google Scholar : PubMed/NCBI
82	Lee M and Partridge NC: Parathyroid hormone activation of matrix metalloproteinase-13 transcription requires the histone acetyltransferase activity of p300 and PCAF and p300-dependent acetylation of PCAF. J Biol Chem. 285:38014–38022. 2010. View Article : Google Scholar : PubMed/NCBI
83	Zhu W, Yang ML, Yang GY, Boden G and Li L: Changes in serum runt-related transcription factor 2 levels after a 6-month treatment with recombinant human parathyroid hormone in patients with osteoporosis. J Endocrinol Invest. 35:602–606. 2012.