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Åke Lernmark

Principal investigator

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Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones

Author

  • O. D. Madsen
  • L. I. Larsson
  • J. F. Rehfeld
  • T. W. Schwartz
  • A. Lernmark
  • A. D. Labrecque
  • D. F. Steiner

Summary, in English

A liver metastasis (MSL) with a remarkable in vitro proliferation potential has been identified in an NEDH rat carrying a transplantable x-ray-induced islet cell tumor. Two insulin-secreting cell lines, MSL-G and MSL-H, with doubling times of 3-5 d were established by repeated limiting dilution cloning. In vivo inoculation of MSL-G cells induced severe hypoglycemia caused by a small but highly heterogeneous tumor as revealed by immunocytochemistry. Whereas most cells stained for the islet hormones, insulin, glucagon, and somatostatin, clustered cells were discovered to contain cholecystokinin (CCK). Additional in vitro-limiting dilution cloning, followed by immunocytochemical characterization, clearly demonstrated the capacity of single cell clones to simultaneously express the same four hormones. Radioimmunoassays with a panel of site-specific antisera of culture supernatants and purified cell extracts showed the MSL-G2 cells to produce, store, and secrete readily detectable amounts of processed and unprocessed CCK. Gastrin was not detected while coexpression of glucagon and CCK were demonstrated. Mutant clones selected for resistance to 6-thioguanine (frequency, 2 x 10-7) and checked for HAT (hypoxanthine, aminopterin, thymidine) sensitivity retained the capacity for multihormone expression. We propose that the MSL tumor contains pluripotent endocrine stem cells. The MSL tumor and the MSL-G2 cells in particular will allow studies of not only CCK biosynthesis and processing but also of mechanisms involved in tumor and islet cell differentiation.

Department/s

  • Diabetes and Celiac Unit

Publishing year

1986-12-01

Language

English

Pages

2025-2034

Publication/Series

Journal of Cell Biology

Volume

103

Issue

5

Document type

Journal article

Publisher

Rockefeller University Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 0021-9525