UM-HACC-2A: MYB-NFIB fusion-positive human adenoid cystic carcinoma cell line

Oral Oncol. 2018 Dec;87:21-28. doi: 10.1016/j.oraloncology.2018.10.012. Epub 2018 Oct 18.

Abstract

Objectives: Limited availability of validated human adenoid cystic carcinoma (ACC) cell lines has hindered the mechanistic understanding of the pathobiology of this malignancy and the development of effective therapies. The purpose of this work was to generate and characterize a human ACC cell line.

Material and methods: Immediately after surgery, a tumor fragment from a minor salivary gland from the tongue of a female Caucasian was minced, dissociated, and a single cell suspension was plated in fibronectin-coated flasks. A culture medium containing bovine brain extract and rhEGF was optimized for these cells. Whole exome sequencing was used to evaluate the presence of MYB-NFIB translocation.

Results: The University of Michigan-Human Adenoid Cystic Carcinoma (UM-HACC)-2A cells showed continuous growth in monolayers for at least 180 in vitro passages while maintaining epithelial morphology. Short-tandem repeat (STR) profiling confirmed a 100% match to patient DNA. Whole exome sequencing revealed the presence of the MYB-NFIB fusion in UM-HACC-2A cells, which was confirmed by PCR analysis. Western blots revealed high expression of epithelial markers (e.g. E-cadherin, EGFR, pan-cytokeratin) and proteins associated with ACC (e.g. c-Myb, p63). Developmental therapeutic studies showed that UM-HACC-2A cells were resistant to cisplatin (IC50 = 44.7 µM) while more responsive to paclitaxel (IC50 = 0.0006 µM). In a pilot study, we observed that UM-HACC-2A cells survived orthotopic transplantation into the submandibular gland. Notably, one of the mice injected with UM-HACC-2A cells exhibited lung metastasis after 6 months.

Conclusion: UM-HACC-2A is a MYB-NFIB fusion-positive ACC cell line that is suitable for mechanistic and developmental therapeutics studies.

Keywords: C-Myb; Experimental models; Experimental therapeutics; Gene fusion; MYB-NFIB; Oncogene; Orthotopic; Salivary gland; Salivary gland cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Adenoid Cystic / drug therapy
  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Paclitaxel / therapeutic use
  • Primary Cell Culture / methods
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / pathology
  • Salivary Glands / pathology
  • Xenograft Model Antitumor Assays / methods

Substances

  • MYB-NFIB fusion protein, human
  • Oncogene Proteins, Fusion
  • Paclitaxel