Heparin-binding EGF-like Growth Factor Enhances the Activity of Invasion and Metastasis in Thyroid Cancer Cells

Overview

Journal Oncol Rep

Specialty Oncology

Date 2013 Aug 7

PMID 23917679

Citations 8

Authors

Ichiro Ota

Shigeki Higashiyama

Takashi Masui

Katsunari Yane

Hiroshi Hosoi

Nariaki Matsuura

Affiliations

Soon will be listed here.

Abstract

Thyroid cancer sometimes contains poorly differentiated components, which have the potential of invasion and metastasis. We evaluated the possible roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, in cell growth and invasion of thyroid cancer cells, and demonstrated that HB-EGF is not only a potent mitogen but also a chemotactic factor in the thyroid cancer cells 8305C and SW579. The HB-EGF-mediated chemotaxis was inhibited by neutralizing antibody against the EGF receptor (EGFR/HER1/ErbB1) or tyrphostin AG1478, a specific inhibitor of the EGFR tyrosine kinase. The HB-EGF mRNA and protein expression was also analyzed using RT-PCR and immunofluorescence methods, respectively. In addition, in clinical immunohistochemical study, increased expression of HB-EGF and its receptors, HER1 and EGFR4 (HER4/ErbB4), was observed in thyroid carcinoma cells. Our findings suggest that HB-EGF acts as a potent paracrine and/or autocrine chemotactic factor as well as a mitogen that mediates HER1 and/or HER4 in the invasion and metastasis of thyroid carcinoma cells, including poorly differentiated papillary carcinomas or undifferentiated/anaplastic carcinomas. These data may aid in the development of novel therapeutic strategies for thyroid cancer.

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References

Besner G, Higashiyama S, Klagsbrun M . Isolation and characterization of a macrophage-derived heparin-binding growth factor. Cell Regul. 1990; 1(11):811-9. PMC: 362848. DOI: 10.1091/mbc.1.11.811. View

Ongusaha P, Kwak J, Zwible A, Macip S, Higashiyama S, Taniguchi N . HB-EGF is a potent inducer of tumor growth and angiogenesis. Cancer Res. 2004; 64(15):5283-90. DOI: 10.1158/0008-5472.CAN-04-0925. View

Aust G, Hofmann A, Laue S, Rost A, Kohler T, Scherbaum W . Human thyroid carcinoma cell lines and normal thyrocytes: expression and regulation of matrix metalloproteinase-1 and tissue matrix metalloproteinase inhibitor-1 messenger-RNA and protein. Thyroid. 1998; 7(5):713-24. DOI: 10.1089/thy.1997.7.713. View

Freeman M, Paul S, Kaefer M, Ishikawa M, Adam R, Renshaw A . Heparin-binding EGF-like growth factor in the human prostate: synthesis predominantly by interstitial and vascular smooth muscle cells and action as a carcinoma cell mitogen. J Cell Biochem. 1998; 68(3):328-38. DOI: 10.1002/(sici)1097-4644(19980301)68:3<328::aid-jcb4>3.0.co;2-w. View

Haugen D, Akslen L, Varhaug J, Lillehaug J . Demonstration of a TGF-alpha-EGF-receptor autocrine loop and c-myc protein over-expression in papillary thyroid carcinomas. Int J Cancer. 1993; 55(1):37-43. DOI: 10.1002/ijc.2910550108. View

Marikovsky M, Breuing K, Liu P, Eriksson E, Higashiyama S, Farber P . Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci U S A. 1993; 90(9):3889-93. PMC: 46411. DOI: 10.1073/pnas.90.9.3889. View

Xing M . Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 2010; 20(7):697-706. PMC: 2935335. DOI: 10.1089/thy.2010.1646. View

Miyagawa J, Higashiyama S, Kawata S, Inui Y, Tamura S, Yamamoto K . Localization of heparin-binding EGF-like growth factor in the smooth muscle cells and macrophages of human atherosclerotic plaques. J Clin Invest. 1995; 95(1):404-11. PMC: 295446. DOI: 10.1172/JCI117669. View

Elenius K, Paul S, Allison G, Sun J, Klagsbrun M . Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 1997; 16(6):1268-78. PMC: 1169725. DOI: 10.1093/emboj/16.6.1268. View

10.

Iwamoto R, Higashiyama S, Mitamura T, Taniguchi N, Klagsbrun M, Mekada E . Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J. 1994; 13(10):2322-30. PMC: 395097. DOI: 10.1002/j.1460-2075.1994.tb06516.x. View

11.

Noguchi S, Aihara T, Nakamori S, Motomura K, Inaji H, Imaoka S . The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Cancer. 1994; 74(5):1595-600. DOI: 10.1002/1097-0142(19940901)74:5<1595::aid-cncr2820740516>3.0.co;2-l. View

12.

Peoples G, Blotnick S, Takahashi K, Freeman M, Klagsbrun M, Eberlein T . T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role. Proc Natl Acad Sci U S A. 1995; 92(14):6547-51. PMC: 41555. DOI: 10.1073/pnas.92.14.6547. View

13.

Raab G, Higashiyama S, Hetelekidis S, Abraham J, Damm D, Ono M . Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor. Biochem Biophys Res Commun. 1994; 204(2):592-7. DOI: 10.1006/bbrc.1994.2500. View

14.

Hashimoto K, Higashiyama S, Asada H, Hashimura E, Kobayashi T, Sudo K . Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes. J Biol Chem. 1994; 269(31):20060-6. View

15.

Higashiyama S, Lau K, Besner G, Abraham J, Klagsbrun M . Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem. 1992; 267(9):6205-12. View

16.

Powell P, Klagsbrun M, Abraham J, Jones R . Eosinophils expressing heparin-binding EGF-like growth factor mRNA localize around lung microvessels in pulmonary hypertension. Am J Pathol. 1993; 143(3):784-93. PMC: 1887209. View

17.

Hofmann A, Laue S, Rost A, Scherbaum W, Aust G . mRNA levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 and of their inhibitors TIMP-2 and TIMP-3 in normal thyrocytes and thyroid carcinoma cell lines. Thyroid. 1998; 8(3):203-14. DOI: 10.1089/thy.1998.8.203. View

18.

Higashiyama S, Iwabuki H, Morimoto C, Hieda M, Inoue H, Matsushita N . Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands. Cancer Sci. 2008; 99(2):214-20. PMC: 11158050. DOI: 10.1111/j.1349-7006.2007.00676.x. View

19.

Ohnishi Y, Inoue H, Furukawa M, Kakudo K, Nozaki M . Heparin-binding epidermal growth factor-like growth factor is a potent regulator of invasion activity in oral squamous cell carcinoma. Oncol Rep. 2012; 27(4):954-8. PMC: 3583476. DOI: 10.3892/or.2011.1616. View

20.

Goodman S, Vollmers H, Birchmeier W . Control of cell locomotion: perturbation with an antibody directed against specific glycoproteins. Cell. 1985; 41(3):1029-38. DOI: 10.1016/s0092-8674(85)80083-0. View