Establishment of clival chordoma cell line MUG-CC1 and lymphoblastoid cells as a model for potential new treatment strategies.

Verena Gellner,Ellen Heitzer,Beate Rinner,Andreas Leithner,Michael Mokry,Bernadette Liegl-Atzwanger,Birgit Lohberger,Peter Valentin Tomazic,Katharina Meditz,Wolfgang Koele

doi:10.1038/srep24195

Abstract

Chordomas are rare malignant tumors that develop from embryonic remnants of the notochord and arise only in the midline from the clivus to the sacrum. Surgery followed by radiotherapy is the standard treatment. As chordomas are resistant to standard chemotherapy, further treatment options are urgently needed. We describe the establishment of a clivus chordoma cell line, MUG-CC1. The cell line is characterized according to its morphology, immunohistochemistry, and growth kinetics. During establishment, cell culture supernatants were collected, and the growth factors HGF, SDF-1, FGF2, and PDGF analyzed using xMAP® technology. A spontaneous lymphoblastoid EBV-positive cell line was also developed and characterized. MUG-CC1 is strongly positive for brachyury, cytokeratin, and S100. The cell line showed gains of the entire chromosomes 7, 8, 12, 13, 16, 18, and 20, and high level gains on chromosomes 1q21–1q24 and 17q21–17q25. During cultivation, there was significant expression of HGF and SDF-1 compared to continuous chordoma cell lines. A new, well-characterized clival chordoma cell line, as well as a non-tumorigenic lymphoblastoid cell line should serve as an in vitro model for the development of potential new treatment strategies for patients suffering from this disease.

Highlights

Chordomas are rare malignant tumors that develop from embryonic remnants of the notochord and arise only in the midline from the clivus to the sacrum
There has been a major surge in chordoma research, thanks to in vitro models developed by several groups, though clival chordoma cells are especially difficult to maintain in long-term cultures[20]
Chordoma cell lines are useful for studying the molecular oncogenesis of these chemo-resistant tumors and will likely support the development of new treatment options for patients suffering from this rare disease

Summary

Introduction

Chordomas are rare malignant tumors that develop from embryonic remnants of the notochord and arise only in the midline from the clivus to the sacrum. We describe the establishment of a clivus chordoma cell line, MUG-CC1. Cell culture supernatants were collected, and the growth factors HGF, SDF-1, FGF2, and. Chordomas are rare malignant bone tumors that are thought to originate from notochord remnants They are typically low-grade, locally invasive tumors. The new personalized treatment options call for in vitro models but clivus chordoma cell cultures are difficult to breed and no cell lines are commercially available. To close this gap, we used a full endoscopic technique and created suitable culture conditions, enabling us to establish the new and unique MUG-CC1clivus chordoma cell line. The HGF/cMet signaling system has been associated with tumorigenesis, disease progression, and invasiveness in many human carcinomas[6,7,8] and www.nature.com/scientificreports/

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