Growth/differentiation factor-15 inhibits differentiation into osteoclasts-A novel factor involved in control of osteoclast differentiation

Differentiation

Volumn 78, Issue 4, 2009, Pages 213-222

  Vaňhara, Petr ^a   Lincová, Eva ^a,b   Kozubík, Alois ^a,b   Jurdic, Pierre ^c   Souček, Karel ^b   Šmarda, Jan ^a  

^a MASARYK UNIVERSITY   (Czech Republic)

^b INSTITUTE OF BIOPHYSICS   (Czech Republic)

^c Univ Lyon 1   (France)

Author keywords

GDF 15; LNCaP; Osteoclast; Prostate cancer; RAW264.7

Indexed keywords

CARBONATE DEHYDRATASE II; CATHEPSIN K; COLONY STIMULATING FACTOR 1; GROWTH DIFFERENTIATION FACTOR 15; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; OSTEOCLAST DIFFERENTIATION FACTOR; SMAD PROTEIN; SYNAPTOPHYSIN;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MATRIX; BONE METASTASIS; CARCINOMA CELL; CELL DIFFERENTIATION; CELL FUNCTION; CELL STRAIN LNCAP; CONTROLLED STUDY; CULTURE MEDIUM; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; MACROPHAGE; MOUSE; NONHUMAN; ONCOGENE C FOS; OSTEOCLAST; OSTEOLYSIS; PRIORITY JOURNAL; PROSTATE ADENOCARCINOMA; PROTEIN DEGRADATION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION;

ACID PHOSPHATASE; ANIMALS; CALCITRIOL; CARBONIC ANHYDRASE II; CATHEPSIN K; CELL DIFFERENTIATION; CELL LINE; CELL LINE, TUMOR; CULTURE MEDIA, CONDITIONED; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMUR; GROWTH DIFFERENTIATION FACTOR 15; HUMANS; ISOENZYMES; MACROPHAGE COLONY-STIMULATING FACTOR; MACROPHAGES; MALE; MICE; MICE, INBRED STRAINS; NF-KAPPA B; OSTEOCLASTS; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-FOS; RANK LIGAND; TIME FACTORS;

EID: 70350398634     PISSN: 03014681     EISSN: 14320436     Source Type: Journal    
DOI: 10.1016/j.diff.2009.07.008     Document Type: Article

References (87)

1. Aliprantis A.O., Ueki Y., Sulyanto R., Park A., Sigrist K.S., Sharma S.M., Ostrowski M.C., Olsen B.R., and Glimcher L.H. NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism. J. Clin. Invest. 118 (2008) 3775-3789
2. Baek S.J., and Eling T.E. Changes in gene expression contribute to cancer prevention by COX inhibitors. Prog. Lipid Res. 45 (2006) 1-16
3. Bauskin A.R., Brown D.A., Kuffner T., Johnen H., Luo X.W., Hunter M., and Breit S.N. Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res. 66 (2006) 4983-4986
4. Beer T.M., and Myrthue A. Calcitriol in the treatment of prostate cancer. Anticancer Res. 26 (2006) 2647-2651
5. Blouin S., Basle M.F., and Chappard D. Interactions between microenvironment and cancer cells in two animal models of bone metastasis. Br. J. Cancer 98 (2008) 809-815
6. Blutt S.E., McDonnell T.J., Polek T.C., and Weigel N.L. Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2. Endocrinology 141 (2000) 10-17
7. Bootcov M.R., Bauskin A.R., Valenzuela S.M., Moore A.G., Bansal M., He X.Y., Zhang H.P., Donnellan M., Mahler S., Pryor K., Walsh B.J., Nicholson R.C., Fairlie W.D., Por S.B., Robbins J.M., and Breit S.N. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc. Natl. Acad. Sci. USA 94 (1997) 11514-11519
8. Boyce B.F., and Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch. Biochem. Biophys. 473 (2008) 139-146
9. Boyle G.M., Pedley J., Martyn A.C., Banducci K.J., Strutton G.M., Brown D.A., Breit S.N., and Parsons P.G. Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. J. Invest. Dermatol. 129 (2009) 383-391
10. Boyle W.J., Simonet W.S., and Lacey D.L. Osteoclast differentiation and activation. Nature 423 (2003) 337-342
11. Bronisz A., Sharma S.M., Hu R., Godlewski J., Tzivion G., Mansky K.C., and Ostrowski M.C. Microphthalmia-associated transcription factor interactions with 14-3-3 modulate differentiation of committed myeloid precursors. Mol. Biol. Cell 17 (2006) 3897-3906
12. Brown D.A., Stephan C., Ward R.L., Law M., Hunter M., Bauskin A.R., Amin J., Jung K., Diamandis E.P., Hampton G.M., Russell P.J., Giles G.G., and Breit S.N. Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis. Clin. Cancer Res. 12 (2006) 89-96
13. Buijs J.T., Rentsch C.A., van der Horst G., van Overveld P.G., Wetterwald A., Schwaninger R., Henriquez N.V., Ten Dijke P., Borovecki F., Markwalder R., Thalmann G.N., Papapoulos S.E., Pelger R.C., Vukicevic S., Cecchini M.G., Lowik C.W., and van der Pluijm G. BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am. J. Pathol. 171 (2007) 1047-1057
14. Cappellen D., Luong-Nguyen N.H., Bongiovanni S., Grenet O., Wanke C., and Susa M. Transcriptional program of mouse osteoclast differentiation governed by the macrophage colony-stimulating factor and the ligand for the receptor activator of NFkappa B. J. Biol. Chem. 277 (2002) 21971-21982
15. Clezardin P., and Teti A. Bone metastasis: pathogenesis and therapeutic implications. Clin. Exp. Metastasis 24 (2007) 599-608
16. Crotti T.N., Sharma S.M., Fleming J.D., Flannery M.R., Ostrowski M.C., Goldring S.R., and McHugh K.P. PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta3 integrin promoter. J. Cell. Physiol. 215 (2008) 636-644
17. Chen Y.L., Lin P.C., Chen S.P., Lin C.C., Tsai N.M., Cheng Y.L., Chang W.L., Lin S.Z., and Harn H.J. Activation of NAG-1 via ERK1/2 mitogen-activated protein kinase revealed a isochaihulactone-triggered apoptotic pathway in human lung cancer A549 cells. J. Pharmacol. Exp. Ther. (2007) (jpet.107.126193)
18. Cher M.L., Towler D.A., Rafii S., Rowley D., Donahue H.J., Keller E., Herlyn M., Cho E.A., and Chung L.W. Cancer interaction with the bone microenvironment: a workshop of the National Institutes of Health Tumor Microenvironment Study Section. Am. J. Pathol. 168 (2006) 1405-1412
19. Chiao J.W., Moonga B.S., Yang Y.M., Kancherla R., Mittelman A., Wu-Wong J.R., and Ahmed T. Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. Br. J. Cancer 83 (2000) 360-365
20. Chung L.W., Baseman A., Assikis V., and Zhau H.E. Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. J. Urol. 173 (2005) 10-20
21. Chung L.W., Huang W.C., Sung S.Y., Wu D., Odero-Marah V., Nomura T., Shigemura K., Miyagi T., Seo S., Shi C., Molitierno J., Elmore J., Anderson C., Isotani S., Edlund M., Hsieh C.L., Wang R., Shehata B., and Zhau H.E. Stromal-epithelial interaction in prostate cancer progression. Clin. Genitourin. Cancer 5 (2006) 162-170
22. Dai J., Hall C.L., Escara-Wilke J., Mizokami A., Keller J.M., and Keller E.T. Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Res. 68 (2008) 5785-5794
23. David J.P., Rincon M., Neff L., Horne W.C., and Baron R. Carbonic anhydrase II is an AP-1 target gene in osteoclasts. J. Cell. Physiol. 188 (2001) 89-97
24. Destaing O., Saltel F., Geminard J.C., Jurdic P., and Bard F. Podosomes display actin turnover and dynamic self-organization in osteoclasts expressing actin-green fluorescent protein. Mol. Biol. Cell 14 (2003) 407-416
25. Emami K.H., and Corey E. When prostate cancer meets bone: control by wnts. Cancer Lett. 253 (2007) 170-179
26. Fujisaki K., Tanabe N., Suzuki N., Kawato T., Takeichi O., Tsuzukibashi O., Makimura M., Ito K., and Maeno M. Receptor activator of NF-kappaB ligand induces the expression of carbonic anhydrase II, cathepsin K, and matrix metalloproteinase-9 in osteoclast precursor RAW264.7 cells. Life Sci. 80 (2007) 1311-1318
27. Futakuchi M., Nannuru K.C., Varney M.L., Sadanandam A., Nakao K., Asai K., Shirai T., Sato S.Y., and Singh R.K. Transforming growth factor-beta signaling at the tumor-bone interface promotes mammary tumor growth and osteoclast activation. Cancer Sci. 100 (2009) 71-81
28. Garimella R., Tague S.E., Zhang J., Belibi F., Nahar N., Sun B.H., Insogna K., Wang J., and Anderson H.C. Expression and synthesis of bone morphogenetic proteins by osteoclasts: a possible path to anabolic bone remodeling. J. Histochem. Cytochem. 56 (2008) 569-577
29. Gingery A., Bradley E.W., Pederson L., Ruan M., Horwood N.J., and Oursler M.J. TGF-beta coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival. Exp. Cell Res. 314 (2008) 2725-2738
30. Goltzman D. Mechanisms of the development of osteoblastic metastases. Cancer 80 (1997) 1581-1587
31. Grigoriadis A.E., Wang Z.Q., Cecchini M.G., Hofstetter W., Felix R., Fleisch H.A., and Wagner E.F. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266 (1994) 443-448
32. Guise T.A., and Chirgwin J.M. Transforming growth factor-beta in osteolytic breast cancer bone metastases. Clin. Orthop. Relat. Res. (2003) S32-S38
33. Hattersley G., and Chambers T.J. Effects of transforming growth factor beta 1 on the regulation of osteoclastic development and function. J. Bone Miner. Res. 6 (1991) 165-172
34. Hofbauer L.C., Dunstan C.R., Spelsberg T.C., Riggs B.L., and Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin d, bone morphogenetic protein-2, and cytokines. Biochem. Biophys. Res. Commun. 250 (1998) 776-781
35. Holen I., Croucher P.I., Hamdy F.C., and Eaton C.L. Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells. Cancer Res. 62 (2002) 1619-1623
36. Horoszewicz J.S., Leong S.S., Kawinski E., Karr J.P., Rosenthal H., Chu T.M., Mirand E.A., and Murphy G.P. LNCaP model of human prostatic carcinoma. Cancer Res. 43 (1983) 1809-1818
37. Hotokezaka H., Sakai E., Kanaoka K., Saito K., Matsuo K., Kitaura H., Yoshida N., and Nakayama K. U0126 and PD98059, specific inhibitors of MEK, accelerate differentiation of RAW264.7 cells into osteoclast-like cells. J. Biol. Chem. 277 (2002) 47366-47372
38. Hu R., Sharma S.M., Bronisz A., Srinivasan R., Sankar U., and Ostrowski M.C. Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors. Mol. Cell. Biol. 27 (2007) 4018-4027
39. Idris A., Mrak E., Greig I., Guidobono F., Ralston S.H., and van 't Hof R. ABD56 causes osteoclast apoptosis by inhibiting the NF[kappa]B and ERK pathways. Biochem. Biophys. Res. Commun. 371 (2008) 94-98
40. Ikeda F., Nishimura R., Matsubara T., Tanaka S., Inoue J., Reddy S.V., Hata K., Yamashita K., Hiraga T., Watanabe T., Kukita T., Yoshioka K., Rao A., and Yoneda T. Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J. Clin. Invest. 114 (2004) 475-484
41. Inoue H., Nishimura K., Oka D., Nakai Y., Shiba M., Tokizane T., Arai Y., Nakayama M., Shimizu K., Takaha N., Nonomura N., and Okuyama A. Prostate cancer mediates osteoclastogenesis through two different pathways. Cancer Lett. 223 (2005) 121-128
42. Ishii J., Kitazawa R., Mori K., McHugh K.P., Morii E., Kondo T., and Kitazawa S. Lipopolysaccharide suppresses RANK gene expression in macrophages by down-regulating PU.1 and MITF. J. Cell. Biochem. 105 (2008) 896-904
43. Jemal A., Siegel R., Ward E., Hao Y., Xu J., Murray T., and Thun M.J. Cancer statistics, 2008. CA Cancer J. Clin. 58 (2008) 71-96
44. Johnen H., Lin S., Kuffner T., Brown D.A., Tsai V.W.-W., Bauskin A.R., Wu L., Pankhurst G., Jiang L., Junankar S., Hunter M., Fairlie W.D., Lee N.J., Enriquez R.F., Baldock P.A., Corey E., Apple F.S., Murakami M.M., Lin E.-J., Wang C., During M.J., Sainsbury A., Herzog H., and Breit S.N. Tumor-induced anorexia and weight loss are mediated by the TGF-[beta] superfamily cytokine MIC-1. Nat. Med. 13 (2007) 1333-1340
45. Kaighn M.E., Narayan K.S., Ohnuki Y., Lechner J.F., and Jones L.W. Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest. Urol. 17 (1979) 16-23
46. Kaneko H., Arakawa T., Mano H., Kaneda T., Ogasawara A., Nakagawa M., Toyama Y., Yabe Y., Kumegawa M., and Hakeda Y. Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. Bone 27 (2000) 479-486
47. Karin M., and Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol. 18 (2000) 621-663
48. Kawada M., Inoue H., Arakawa M., and Ikeda D. Transforming growth factor-beta1 modulates tumor-stromal cell interactions of prostate cancer through insulin-like growth factor-I. Anticancer Res. 28 (2008) 721-730
49. Kim K.K., Lee J.J., Yang Y., You K.H., and Lee J.H. Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells. Carcinogenesis 29 (2008) 704-712
50. Kingsley L.A., Fournier P.G., Chirgwin J.M., and Guise T.A. Molecular biology of bone metastasis. Mol. Cancer Ther. 6 (2007) 2609-2617
51. Koeneman K.S., Yeung F., and Chung L.W. Osteomimetic properties of prostate cancer cells: a hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. Prostate 39 (1999) 246-261
52. Kondo T., Kitazawa R., Maeda S., and Kitazawa S. 1 alpha,25 dihydroxyvitamin D-3 rapidly regulates the mouse osteoprotegerin gene through dual pathways. J. Bone Miner. Res. 19 (2004) 1411-1419
53. Kubota K., Sakikawa C., Katsumata M., Nakamura T., and Wakabayashi K. Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor. J. Bone Miner. Res. 17 (2002) 257-265
54. Lambert J.R., Kelly J.A., Shim M., Huffer W.E., Nordeen S.K., Baek S.J., Eling T.E., and Lucia M.S. Prostate derived factor in human prostate cancer cells: gene induction by vitamin D via a p53-dependent mechanism and inhibition of prostate cancer cell growth. J. Cell. Physiol. 208 (2006) 566-574
55. Levy C., Khaled M., and Fisher D.E. MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol. Med. 12 (2006) 406-414
56. Li N., and Karin M. Signaling pathways leading to nuclear factor-kappa B activation. Methods Enzymol. 319 (2000) 273-279
57. Liao J., and McCauley L.K. Skeletal metastasis: established and emerging roles of parathyroid hormone related protein (PTHrP). Cancer Metastasis Rev. 25 (2006) 559-571
58. Logothetis C.J., and Lin S.H. Osteoblasts in prostate cancer metastasis to bone. Nat. Rev. Cancer 5 (2005) 21-28
59. Massague J. A very private TGF-beta receptor embrace. Mol. Cell 29 (2008) 149-150
60. Massey H.M., Scopes J., Horton M.A., and Flanagan A.M. Transforming growth factor-beta1 (TGF-beta) stimulates the osteoclast-forming potential of peripheral blood hematopoietic precursors in a lymphocyte-rich microenvironment. Bone 28 (2001) 577-582
61. Morrissey C., and Vessella R.L. The role of tumor microenvironment in prostate cancer bone metastasis. J. Cell Biochem. 101 (2007) 873-886
62. Newman D., Sakaue M., Koo J.S., Kim K.S., Baek S.J., Eling T., and Jetten A.M. Differential regulation of nonsteroidal anti-inflammatory drug-activated gene in normal human tracheobronchial epithelial and lung carcinoma cells by retinoids. Mol. Pharmacol. 63 (2003) 557-564
63. Noorali S., Kurita T., Woolcock B., de Algara T.R., Lo M., Paralkar V., Hoodless P., and Vielkind J. Dynamics of expression of growth differentiation factor 15 in normal and PIN development in the mouse. Differentiation 75 (2007) 325-336
64. Pang M., Martinez A.F., Fernandez I., Balkan W., and Troen B.R. AP-1 stimulates the cathepsin K promoter in RAW 264.7 cells. Gene 403 (2007) 151-158
65. Pfaffl M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucl. Acids Res. 29 (2001) e45
66. Polek T.C., Stewart L.V., Ryu E.J., Cohen M.B., Allegretto E.A., and Weigel N.L. p53 Is required for 1,25-dihydroxyvitamin D3-induced G0 arrest but is not required for G1 accumulation or apoptosis of LNCaP prostate cancer cells. Endocrinology 144 (2003) 50-60
67. Rao A., Woodruff R.D., Wade W.N., Kute T.E., and Cramer S.D. Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth. J. Nutr. 132 (2002) 3191-3194
68. Raschke W.C., Baird S., Ralph P., and Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell 15 (1978) 261-267
69. Roudier M.P., True L.D., Higano C.S., Vesselle H., Ellis W., Lange P., and Vessella R.L. Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. Hum. Pathol. 34 (2003) 646-653
70. Roudier M.P., Vesselle H., True L.D., Higano C.S., Ott S.M., King S.H., and Vessella R.L. Bone histology at autopsy and matched bone scintigraphy findings in patients with hormone refractory prostate cancer: the effect of bisphosphonate therapy on bone scintigraphy results. Clin. Exp. Metastasis 20 (2003) 171-180
71. Selander K.S., Brown D.A., Sequeiros G.B., Hunter M., Desmond R., Parpala T., Risteli J., Breit S.N., and Jukkola-Vuorinen A. Serum macrophage inhibitory cytokine-1 concentrations correlate with the presence of prostate cancer bone metastases. Cancer Epidemiol. Biomarkers Prev. 16 (2007) 532-537
72. Sevcikova S., Soucek K., Kubala L., Bryja V., and Smarda J. Differential effects of v-Jun and c-Jun proteins on v-myb-transformed monoblasts. Cell. Mol. Life Sci. 59 (2002) 1690-1705
73. Sharma S.M., Bronisz A., Hu R., Patel K., Mansky K.C., Sif S., and Ostrowski M.C. MITF and PU.1 recruit p38 MAPK and NFATc1 to target genes during osteoclast differentiation. J. Biol. Chem. 282 (2007) 15921-15929
74. Smith M.R. Osteoclast targeted therapy for prostate cancer: bisphosphonates and beyond. Urol. Oncol. 26 (2008) 420-425
75. Stephan C., Xu C., Brown D.A., Breit S.N., Michael A., Nakamura T., Diamandis E.P., Meyer H., Cammann H., and Jung K. Three new serum markers for prostate cancer detection within a percent free PSA-based artificial neural network. Prostate 66 (2006) 651-659
76. Stewart L.V., and Weigel N.L. Vitamin D and prostate cancer. Exp. Biol. Med. (Maywood) 229 (2004) 277-284
77. Stewart L.V., and Weigel N.L. Role of insulin-like growth factor binding proteins in 1alpha, 25-dihydroxyvitamin D(3)-induced growth inhibition of human prostate cancer cells. Prostate 64 (2005) 9-19
78. Strelau J., Schmeer C., Peterziel H., Sackmann T., Herold-Mende C., Steiner H., Weller M., and Unsicker K. Expression and putative functions of GDF-15, a member of the TGF-beta superfamily, in human glioma and glioblastoma cell lines. Cancer Lett. 270 (2008) 30-39
79. Sung S.Y., Hsieh C.L., Wu D., Chung L.W., and Johnstone P.A. Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance. Curr. Probl. Cancer 31 (2007) 36-100
80. Swanson C., Lorentzon M., Conaway H.H., and Lerner U.H. Glucocorticoid regulation of osteoclast differentiation and expression of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvarial bones. Endocrinology 147 (2006) 3613-3622
81. Van Huyen J.P., Cheval L., Bloch-Faure M., Belair M.F., Heudes D., Bruneval P., and Doucet A. GDF15 triggers homeostatic proliferation of acid-secreting collecting duct cells. J. Am. Soc. Nephrol. 19 (2008) 1965-1974
82. Wakchoure S., Swain T.M., Hentunen T.A., Bauskin A.R., Brown D.A., Breit S.N., Vuopala K.S., Harris K.W., and Selander K.S. Expression of macrophage inhibitory cytokine-1 in prostate cancer bone metastases induces osteoclast activation and weight loss. Prostate (2009)
83. Wei S., and Siegal G.P. Mechanisms modulating inflammatory osteolysis: a review with insights into therapeutic targets. Pathol.-Res. Pract. 204 (2008) 695-706
84. Wilson L.C., Baek S.J., Call A., and Eling T.E. Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is induced by genistein through the expression of p53 in colorectal cancer cells. Int. J. Cancer 105 (2003) 747-753
85. Yang H., Filipovic Z., Brown D., Breit S.N., and Vassilev L.T. Macrophage inhibitory cytokine-1: a novel biomarker for p53 pathway activation. Mol. Cancer Ther. 2 (2003) 1023-1029
86. Zhang L., Yang X., Pan H.Y., Zhou X.J., Li J., Chen W.T., Zhong L.P., and Zhang Z.Y. Expression of growth differentiation factor 15 is positively correlated with histopathological malignant grade and in vitro cell proliferation in oral squamous cell carcinoma. Oral Oncol. (2008)
87. Zimmers T.A., Jin X., Hsiao E.C., Perez E.A., Pierce R.H., Chavin K.D., and Koniaris L.G. Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. J. Surg. Res. 130 (2006) 45-51