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. 2013 Jan;187(1):6-14.
doi: 10.1016/j.jviromet.2012.10.001. Epub 2012 Oct 18.

Characterization of an early passage Merkel cell polyomavirus-positive Merkel cell carcinoma cell line, MS-1, and its growth in NOD scid gamma mice

Anna Guastafierro  1 , Huichen Feng, Mamie Thant, John M Kirkwood, Yuan Chang, Patrick S Moore, Masahiro Shuda
Affiliations

Characterization of an early passage Merkel cell polyomavirus-positive Merkel cell carcinoma cell line, MS-1, and its growth in NOD scid gamma mice

Anna Guastafierro et al. J Virol Methods. 2013 Jan.

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high mortality rate. The majority of MCC (70-80%) harbor clonally integrated Merkel cell polyomavirus (MCV) in the tumor genome and express viral T antigen oncoproteins. The characterization of an early passage MCV-positive MCC cell line MS-1 is described, and its cellular, immunohistochemical, and virological features to MCV-negative (UISO, MCC13, and MCC26) and MCV-positive cell lines (MKL-1 and MKL-2) were compared. The MS-1 cellular genome harbors integrated MCV, which preserves an identical viral sequence from its parental tumor. Neither VP2 gene transcripts nor VP1 protein are detectable in MS-1 or other MCV-positive MCC cell lines tested. Mapping of viral and cellular integration sites in MS-1 and MCC tumor samples demonstrates no consistent viral or cellular gene integration locus. All MCV-positive cell lines show cytokeratin 20 positivity and grow in suspension. When injected subcutaneously into NOD scid gamma (NSG) mice, MS-1 forms a discrete macroscopic tumor. Immunophenotypic analysis of the MS-1 cell line and xenografts in mice show identical profiles to the parental tumor biopsy. Hence, MS-1 is an early passage cell line that provides a useful in vitro model to characterize MCV-positive MCC.

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Figures

Fig. 1
Fig. 1. Morphological features of MCC cell lines
MCV-positive cell lines MS-1 (A), MKL-1 (B), and MKL-2 (C) grow in floating aggregates in cell culture, whereas MCV-negative cell lines UISO (D), MCC13 (E), and MCC26 (F) are adherent cells.
Fig. 2
Fig. 2. MS-1 harbors clonally integrated MCV, and expresses viral T antigen proteins
(A) Southern blot analysis of MCV-positive cell lines shows clonally integrated viral genomes. (B) The MCV-positive MCC cell lines MS-1, MKL-1 and MKL-2 have C-terminal LT truncations as determined by direct sequencing performed on genomic DNA. LT protein sizes correspond to 428 aa, 330 aa, and 275 aa, respectively. (C) Western blotting using antibodies CM2B4 for LT and CM8E6 as well as CM5E1 for sT shows differences in size of LT proteins from different MCV-positive MCC cell lines, whereas sT size is the same. The CM2B4 antibody picks up a faint non-specific band in MCV-negative MCC cell lines (marked *).
Fig. 3
Fig. 3. MS-1 xenograft model
Tumor volume graph represents average tumor volumes of 5 animals for each MS-1 and MKL-1 cell lines. (B) Immunoblot analysis of MS-1 and MKL-1 xenograft tumors shows LT as well as sT protein expression in vivo. Three separate xenograft tumor lysates were prepared for each cell line; one representative is shown here. (C) Immunohistochemical analysis of MS-1 xenograft tumors validates LT protein expression and nuclear localization (CM2B4), as well as CK20 positivity in vivo.
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