Characterization of sarcoma-like cells derived from endarterectomized tissues from patients with CTEPH and establishment of a mouse model of pulmonary artery intimal sarcoma

Jujo,Takayuki; Sakao,Seiichiro; Kantake,Masashi; Maruoka,Miki; Tanabe,Nobuhiro; Kasahara,Yasunori; Kurosu,Katsushi; Masuda,Masahisa; Harigaya,Kenichi; Tatsumi,Koichiro

doi:10.3892/ijo.2012.1493

Characterization of sarcoma-like cells derived from endarterectomized tissues from patients with CTEPH and establishment of a mouse model of pulmonary artery intimal sarcoma

Authors:
- Takayuki Jujo
- Seiichiro Sakao
- Masashi Kantake
- Miki Maruoka
- Nobuhiro Tanabe
- Yasunori Kasahara
- Katsushi Kurosu
- Masahisa Masuda
- Kenichi Harigaya
- Koichiro Tatsumi
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Affiliations: Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan, Chiba Medical Center, National Hospital Organization, Chuo-ku, Chiba 260-8606, Japan, Department of Molecular and Tumor Pathology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
Published online on: May 22, 2012 https://doi.org/10.3892/ijo.2012.1493
Pages: 701-711

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Abstract

In general, intravascular thrombus formation in the pulmonary arteries is considered to be the most common cause of chronic thromboembolic pulmonary hypertension (CTEPH). The current mainstay of therapy for patients with CTEPH is pulmonary endarterectomy (PEA). Recently, the existence of myofibroblast-like cells in endarterectomized tissues has been demonstrated. At the 2nd passage of these myofibroblast-like cells, a pleomorphic cell type was isolated. Pulmonary intimal sarcoma is a very uncommon neoplastic tumor thought to originate from subendothelial-mesenchymal cells of the pulmonary vascular wall. Because these pleomorphic cells were isolated from the pulmonary vascular beds, it is believed that the analysis of these cells may contribute to the understanding of pulmonary intimal sarcoma. We isolated cells from the endarterectomized tissue from patients with CTEPH and identified one type as sarcoma-like cells (SCLs). The SCLs were characterized as hyperproliferative, anchorage-independent, invasive and serum-independent. Moreover, C.B-17/lcr-scid/scidJcl mice injected subcutaneously with SCLs developed solid, undifferentiated tumors at the site of injection, and those injected intravenously with SCLs via the tail vein developed tumors which grew along the intimal surface of the pulmonary vessels, thus, demonstrating the high tumorigenic potential of these cells. The behavior of SCLs indicated that these cells may have a vascular cell-like potential which can affiliate them with the intimal surface of the pulmonary artery, and which may be shared with pulmonary intimal sarcoma. A further investigation of this mouse model with SCLs may elucidate the mechanism(s) underlying the development of pulmonary intimal sarcoma.

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1	Fedullo PF, Kerr KM, Auger WR, Jamieson SW and Kapelanski DP: Chronic thromboembolic pulmonary hypertension. Semin Respir Crit Care Med. 21:563–574. 2000. View Article : Google Scholar : PubMed/NCBI
2	Moser KM, Daily PO, Peterson K, Dembitsky W, Vapnek JM, Shure D, Utley J and Archibald C: Thromboendarterectomy for chronic, major vessel thromboembolic pulmonary hypertension: immediate and long-term results in 42 patients. Ann Intern Med. 107:560–565. 1987. View Article : Google Scholar : PubMed/NCBI
3	Jamieson SW, Kapelanski DP, Sakakibara N, Manecke GR, Thistlethwaite PA, Kerr KM, Channick RN, Fedullo PF and Auger WR: Pulmonary endarterectomy: experience and lessons learned in 1,500 cases. Ann Thorac Surg. 76:1457–1464. 2003. View Article : Google Scholar : PubMed/NCBI
4	Maruoka M, Sakao S, Kantake M, Tanabe N, Kasahara Y, Kurosu K, Takiguchi Y, Masuda M, Yoshino I, Voelkel NF and Tatsumi K: Characterization of myofibroblasts in chronic thromboembolic pulmonary hypertension. Int J Cardiol. Mar 14–2011, (Epub ahead of print).
5	Yao W, Firth AL, Sacks RS, Ogawa A, Auger WR, Fedullo PF, Madani MM, Lin GY, Sakakibara N, Thistlethwaite PA, Jamieson SW, Rubin LJ and Yuan JX: Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 296:L870–L878. 2009. View Article : Google Scholar : PubMed/NCBI
6	Firth AL, Yao W, Ogawa A, Madani MM, Lin GY and Yuan JX: Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertension. Am J Physiol Cell Physiol. 298:C1217–C1225. 2010. View Article : Google Scholar
7	Sakao S, Hao H, Tanabe N, Kasahara Y, Kurosu K and Tatsumi K: Endothelial-like cells in chronic thromboembolic pulmonary hypertension: crosstalk with myofibroblast-like cells. Respir Res. 12:1092011. View Article : Google Scholar : PubMed/NCBI
8	Bloomberg RD, Butany JW, Cusimano RJ and Leask RL: Primary cardiac sarcoma involving the pulmonary artery and valve. Can J Cardiol. 19:843–847. 2003.PubMed/NCBI
9	Bode-Lesniewska B, Zhao J, Speel EJ, Biraima AM, Turina M, Komminoth P and Heitz PU: Gains of 12q13–14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery. Virchows Arch. 438:57–65. 2001.
10	Gaumann A, Petrow P, Mentzel T, Mayer E, Dahm M, Otto M, Kirkpatrick CJ and Kriegsmann J: Osteopontin expression in primary sarcomas of the pulmonary artery. Virchows Arch. 439:668–674. 2001. View Article : Google Scholar : PubMed/NCBI
11	Burke AP and Virmani R: Sarcomas of the great vessels. Cancer. 71:1761–1773. 1993. View Article : Google Scholar : PubMed/NCBI
12	McGlennen RC, Manivel JC, Stanley SJ, Slater DL, Wick MR and Dehner LP: Pulmonary artery trunk sarcoma: a clinicopathologic, ultrastructural, and immunohistochemical study of four cases. Mod Pathol. 2:486–494. 1989.PubMed/NCBI
13	Hanahan D and Weinberg R: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar
14	Rai PR, Cool CD, King JA, Stevens T, Burns N, Winn RA, Kasper M and Voelkel NF: The cancer paradigm of severe angioproliferative pulmonary hypertension. Am J Respir Crit Care Med. 178:558–564. 2008. View Article : Google Scholar : PubMed/NCBI
15	Sakao S and Tatsumi K: Vascular remodeling in pulmonary arterial hypertension: multiple cancer-like pathways and possible treatment modalities. Int J Cardiol. 147:4–12. 2011. View Article : Google Scholar : PubMed/NCBI
16	Loebinger MR, Sage EK and Janes SM: Mesenchymal stem cells as vectors for lung disease. Proc Am Thorac Soc. 5:711–716. 2008. View Article : Google Scholar : PubMed/NCBI
17	Aguilar S, Nye E, Chan J, Loebinger M, Spencer-Dene B, Fisk N, Stamp G, Bonnet D and Janes SM: Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells. 25:1586–1594. 2007. View Article : Google Scholar : PubMed/NCBI
18	Gu J, Fujibayashi A, Yamada KM and Sekiguchi K: Laminin-10/11 and fibronectin differentially prevent apoptosis induced by serum removal via phosphatidylinositol 3-kinase/Akt- and MEK1/ERK-dependent pathways. J Biol Chem. 277:19922–19928. 2002. View Article : Google Scholar : PubMed/NCBI
19	Adachi Y, Yamamoto H, Itoh F, Hinoda Y, Okada Y and Imai K: Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers. Gut. 45:252–258. 1999. View Article : Google Scholar : PubMed/NCBI
20	Yamamoto H, Iku S, Adachi Y, Imsumran A, Taniguchi H, Nosho K, Min Y, Horiuchi S, Yoshida M, Itoh F and Imai K: Association of trypsin expression with tumour progression and matrilysin expression in human colorectal cancer. J Pathol. 199:176–184. 2003. View Article : Google Scholar : PubMed/NCBI
21	Bolon I, Devouassoux M, Robert C, Moro D, Brambilla C and Brambilla E: Expression of urokinase-type plasminogen activator, stromelysin 1, stromelysin 3, and matrilysin genes in lung carcinomas. Am J Pathol. 150:1619–1629. 1997.PubMed/NCBI
22	Heppner KJ, Matrisian LM, Jensen RA and Rodgers WH: Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol. 149:273–282. 1996.PubMed/NCBI
23	Yamamoto H, Adachi Y, Itoh F, Iku S, Matsuno K, Kusano M, Arimura Y, Endo T, Hinoda Y, Hosokawa M and Imai K: Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res. 59:3313–3316. 1999.PubMed/NCBI