Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Orthopaedics and Related Research®
Published in: Clinical Orthopaedics and Related Research® 9/2008

01-09-2008 | Symposium: Molecular Genetics in Sarcoma

Expression of Macrophage Migration Inhibitory Factor Relates to Survival in High-grade Osteosarcoma

Authors: Ilkyu Han, MD, PhD, Mi Ra Lee, BS, Kwang Woo Nam, MD, Joo Han Oh, MD, PhD, Kyung Chul Moon, MD, PhD, Han-Soo Kim, MD, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 9/2008

Login to get access

Abstract

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is implicated in many aspects of tumor progression, including cell proliferation, invasion, and angiogenesis. We asked if MIF expression predicts survival and if it is associated with angiogenesis and cell invasion in osteosarcoma. We performed immunohistochemistry for MIF expression in prechemotherapy biopsy specimens of 58 patients with osteosarcoma. To investigate the role of MIF in angiogenesis, microvessel density was measured and compared with MIF expression. We also treated osteosarcoma cell lines (U2-OS and MG63) with MIF and measured vascular endothelial growth factor, a potent proangiogenic factor, by enzyme-linked immunosorbent assay. To study the role of MIF in cell invasion, Boyden chamber assay was performed after knockdown of MIF by short interfering RNA. MIF independently predicted overall survival and metastasis-free survival. MIF expression correlated with microvessel density and induced a dose-dependent increase in vascular endothelial growth factor. Knockdown of MIF by short interfering RNA resulted in decreased cell invasion. These results suggest MIF could serve as a prognostic marker and a potential therapeutic target for osteosarcoma.
Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
Literature
1.
Bacher M, Schrader J, Thompson N, Kuschela K, Gemsa D, Waeber G, Schlegel J. Up-regulation of macrophage migration inhibitory factor gene and protein expression in glial tumor cells during hypoxic and hypoglycemic stress indicates a critical role for angiogenesis in glioblastoma multiforme. Am J Pathol. 2003;162:11–17.PubMed
2.
Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol. 1994;12:423–431.PubMed
3.
Ek ET, Dass CR, Contreras KG, Choong PF. Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis. Cancer Gene Ther. 2007;14:616–626.PubMedCrossRef
4.
Enneking W. Staging musculoskeletal tumors. In: Enneking W, ed. Musculoskeletal Tumor Surgery. New York: Churchill Livingstone; 1983:69–88.
5.
Gorlick R, Anderson P, Andrulis I, Arndt C, Beardsley GP, Bernstein M, Bridge J, Cheung NK, Dome JS, Ebb D, Gardner T, Gebhardt M, Grier H, Hansen M, Healey J, Helman L, Hock J, Houghton J, Houghton P, Huvos A, Khanna C, Kieran M, Kleinerman E, Ladanyi M, Lau C, Malkin D, Marina N, Meltzer P, Meyers P, Schofield D, Schwartz C, Smith MA, Toretsky J, Tsokos M, Wexler L, Wigginton J, Withrow S, Schoenfeldt M, Anderson B. Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. Clin Cancer Res. 2003;9:5442–5453.PubMed
6.
Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, Nagasue N. Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer. 2005;103:588–598.PubMedCrossRef
7.
Hoang BH, Kubo T, Healey JH, Sowers R, Mazza B, Yang R, Huvos AG, Meyers PA, Gorlick R. Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. Int J Cancer. 2004;109:106–111.PubMedCrossRef
8.
Kager L, Zoubek A, Potschger U, Kastner U, Flege S, Kempf-Bielack B, Branscheid D, Kotz R, Salzer-Kuntschik M, Winkelmann W, Jundt G, Kabisch H, Reichardt P, Jurgens H, Gadner H, Bielack SS. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2003;21:2011–2018.PubMedCrossRef
9.
Kamimura A, Kamachi M, Nishihira J, Ogura S, Isobe H, Dosaka-Akita H, Ogata A, Shindoh M, Ohbuchi T, Kawakami Y. Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung. Cancer. 2000;89:334–341.PubMedCrossRef
10.
Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res. 2000;6:572–577.PubMed
11.
Kreuter M, Bieker R, Bielack SS, Auras T, Buerger H, Gosheger G, Jurgens H, Berdel WE, Mesters RM. Prognostic relevance of increased angiogenesis in osteosarcoma. Clin Cancer Res. 2004;10:8531–8537.PubMedCrossRef
12.
Laverdiere C, Hoang BH, Yang R, Sowers R, Qin J, Meyers PA, Huvos AG, Healey JH, Gorlick R. Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res. 2005;11:2561–2567.PubMedCrossRef
13.
Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, Memon MA, Weeden S, Uscinska BM, van Glabbeke M, Kirkpatrick A, Hauben EI, Craft AW, Taminiau AH. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007;99:112–128.PubMedCrossRef
14.
Luu HH, Zhou L, Haydon RC, Deyrup AT, Montag AG, Huo D, Heck R, Heizmann CW, Peabody TD, Simon MA, He TC. Increased expression of S100A6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma. Cancer Lett. 2005;229:135–148.PubMedCrossRef
15.
Marina N, Gebhardt M, Teot L, Gorlick R. Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 2004;9:422–441.PubMedCrossRef
16.
Meyer-Siegler K, Hudson PB. Enhanced expression of macrophage migration inhibitory factor in prostatic adenocarcinoma metastases. Urology. 1996;48:448–452.PubMedCrossRef
17.
Meyer-Siegler KL, Iczkowski KA, Vera PL. Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer. BMC Cancer. 2005;5:73.PubMedCrossRef
18.
Meyer-Siegler KL, Leifheit EC, Vera PL. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells. BMC Cancer. 2004;4:34.PubMedCrossRef
19.
Mitchell RA. Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal. 2004;16:13–19.PubMedCrossRef
20.
Munaut C, Boniver J, Foidart JM, Deprez M. Macrophage migration inhibitory factor (MIF) expression in human glioblastomas correlates with vascular endothelial growth factor (VEGF) expression. Neuropathol Appl Neurobiol. 2002;28:452–460.PubMedCrossRef
21.
Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y, Todo S. Macrophage migration inhibitory factor (MIF): its potential role in tumor growth and tumor-associated angiogenesis. Ann NY Acad Sci. 2003;995:171–182.PubMedCrossRef
22.
Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, Wong J. Macrophage migration inhibitory factor stimulates angiogenic factor expression and correlates with differentiation and lymph node status in patients with esophageal squamous cell carcinoma. Ann Surg. 2005;242:55–63.PubMedCrossRef
23.
Ren Y, Tsui HT, Poon RT, Ng IO, Li Z, Chen Y, Jiang G, Lau C, Yu WC, Bacher M, Fan ST. Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma. Int J Cancer. 2003;107:22–29.PubMedCrossRef
24.
Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, Marcove RC, Lane JM, Mehta B, Urban C. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221–1230.PubMedCrossRef
25.
Sun B, Nishihira J, Yoshiki T, Kondo M, Sato Y, Sasaki F, Todo S. Macrophage migration inhibitory factor promotes tumor invasion and metastasis via the Rho-dependent pathway. Clin Cancer Res. 2005;11:1050–1058.PubMed
26.
Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY. Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 2002;38:1564–1579.PubMedCrossRef
27.
Ward WG, Mikaelian K, Dorey F, Mirra JM, Sassoon A, Holmes EC, Eilber FR, Eckardt JJ. Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases. J Clin Oncol. 1994;12:1849–1858.PubMed
28.
White ES, Flaherty KR, Carskadon S, Brant A, Iannettoni MD, Yee J, Orringer MB, Arenberg DA. Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: role in angiogenesis and prognosis. Clin Cancer Res. 2003;9:853–860.PubMed
29.
Wilson JM, Coletta PL, Cuthbert RJ, Scott N, MacLennan K, Hawcroft G, Leng L, Lubetsky JB, Jin KK, Lolis E, Medina F, Brieva JA, Poulsom R, Markham AF, Bucala R, Hull MA. Macrophage migration inhibitory factor promotes intestinal tumorigenesis. Gastroenterology. 2005;129:1485–1503.PubMedCrossRef
30.
Yao K, Shida S, Selvakumaran M, Zimmerman R, Simon E, Schick J, Haas NB, Balke M, Ross H, Johnson SW, O’Dwyer PJ. Macrophage migration inhibitory factor is a determinant of hypoxia-induced apoptosis in colon cancer cell lines. Clin Cancer Res. 2005;11:7264–7272.PubMedCrossRef
Metadata
Title
Expression of Macrophage Migration Inhibitory Factor Relates to Survival in High-grade Osteosarcoma
Authors
Ilkyu Han, MD, PhD
Mi Ra Lee, BS
Kwang Woo Nam, MD
Joo Han Oh, MD, PhD
Kyung Chul Moon, MD, PhD
Han-Soo Kim, MD, PhD
Publication date
01-09-2008
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 9/2008
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-008-0333-1

Other articles of this Issue 9/2008

Clinical Orthopaedics and Related Research® 9/2008 Go to the issue

Original Article

The Biceps Crease Interval for Diagnosing Complete Distal Biceps Tendon Ruptures

Original Article

Lewis A. Sayre: The First Professor of Orthopaedic Surgery in America

Original Article

Radiographic Joint Space Width in Patients with Crowe Type-I Dysplastic Hips

Symposium: Molecular Genetics in Sarcoma

Dominant Negative LRP5 Decreases Tumorigenicity and Metastasis of Osteosarcoma in an Animal Model

Symposium: Molecular Genetics in Sarcoma

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Residents' Corner

Statistics in Brief: The Importance of Sample Size in the Planning and Interpretation of Medical Research