Schwannomatosis, a rare form of
neurofibromatosis, is characterized predominantly by multiple, often painful,
schwannomas throughout the peripheral nervous system. The current standard of care for
schwannomatosis is surgical resection. A major obstacle to
schwannomatosis research is the lack of robust tumor cell lines. There is a great need for mechanistic and
drug discovery studies of
schwannomatosis, yet appropriate tools are not currently available.
Schwannomatosis tumors are difficult to grow in culture as they survive only a few passages before senescence. Our lab has extensive experience in establishing primary and immortalized human Schwann cell cultures from normal tissue that retain their phenotypes after immortalization. Therefore we took on the challenge of creating immortalized human Schwann cell lines derived from
tumors from
schwannomatosis patients. We have established and fully characterized 2
schwannomatosis cell lines from 2 separate patients using SV40 virus
large T antigen. One patient reported
pain and the other did not. The
schwannomatosis cell lines were stained with S100B
antibodies to confirm Schwann cell identity. The
schwannomatosis cells also expressed the Schwann cell markers, p75NTR, S100B, and
NGF after multiple passages. Cell morphology was retained following multiple passaging and freeze/ thaw cycles. Gene expression microarray analysis was used to compare the cell lines with their respective parent
tumors. No differences in key genes were detected, with the exception that several cell cycle regulators were upregulated in the
schwannomatosis cell lines when compared to their parent
tumors. This upregulation was apparently a product of cell culturing, as the
schwannomatosis cells exhibited the same expression pattern of cell cycle regulatory genes as normal primary human Schwann cells. Cell growth was also similar between normal primary and immortalized
tumor cells in culture. Accurate cell lines derived directly from human
tumors will serve as invaluable tools for advancing
schwannomatosis research, including
drug screening.