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

Madsen, O. D. ; Larsson, L. I. ; Rehfeld, J. F. ; Schwartz, T. W. ; Lernmark, A. LU orcid ; Labrecque, A. D. and Steiner, D. F. (1986) In Journal of Cell Biology 103(5). p.2025-2034
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cell Biology
volume
103
issue
5
pages
10 pages
publisher
Rockefeller University Press
external identifiers
  • scopus:0022976649
  • pmid:2877997
ISSN
0021-9525
DOI
10.1083/jcb.103.5.2025
language
English
LU publication?
yes
id
486c592a-6756-4f9f-b284-cda8ed8ba6e1
date added to LUP
2019-09-16 12:32:41
date last changed
2024-03-13 08:17:09
@article{486c592a-6756-4f9f-b284-cda8ed8ba6e1,
  abstract     = {{<p>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<sup>-7</sup>) 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.</p>}},
  author       = {{Madsen, O. D. and Larsson, L. I. and Rehfeld, J. F. and Schwartz, T. W. and Lernmark, A. and Labrecque, A. D. and Steiner, D. F.}},
  issn         = {{0021-9525}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{5}},
  pages        = {{2025--2034}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Cell Biology}},
  title        = {{Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones}},
  url          = {{http://dx.doi.org/10.1083/jcb.103.5.2025}},
  doi          = {{10.1083/jcb.103.5.2025}},
  volume       = {{103}},
  year         = {{1986}},
}