Establishment of a human gastrinoma in nude mice

James R. Upp, Judith L. Trudel, Courtney Townsend, Robert W. Alexander, Srinivasan Rajaraman, William H. Nealon, George H. Greeley, James C. Thompson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 μg/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 μg/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 ± 93 mg) was significantly greater than control fundic weight (180 ± 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.

Original languageEnglish (US)
Pages (from-to)1037-1045
Number of pages9
JournalSurgery
Volume104
Issue number6
StatePublished - 1988

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Gastrinoma
Gastrins
Nude Mice
Secretin
Octreotide
Neoplasms
Serum
Neoplasm Metastasis
Zollinger-Ellison Syndrome
Weight-Bearing
Somatostatin
Intraperitoneal Injections
Hyperplasia
Radioimmunoassay
Stomach
Histology

ASJC Scopus subject areas

  • Surgery

Cite this

Upp, J. R., Trudel, J. L., Townsend, C., Alexander, R. W., Rajaraman, S., Nealon, W. H., ... Thompson, J. C. (1988). Establishment of a human gastrinoma in nude mice. Surgery, 104(6), 1037-1045.

Establishment of a human gastrinoma in nude mice. / Upp, James R.; Trudel, Judith L.; Townsend, Courtney; Alexander, Robert W.; Rajaraman, Srinivasan; Nealon, William H.; Greeley, George H.; Thompson, James C.

In: Surgery, Vol. 104, No. 6, 1988, p. 1037-1045.

Research output: Contribution to journalArticle

Upp, JR, Trudel, JL, Townsend, C, Alexander, RW, Rajaraman, S, Nealon, WH, Greeley, GH & Thompson, JC 1988, 'Establishment of a human gastrinoma in nude mice', Surgery, vol. 104, no. 6, pp. 1037-1045.
Upp JR, Trudel JL, Townsend C, Alexander RW, Rajaraman S, Nealon WH et al. Establishment of a human gastrinoma in nude mice. Surgery. 1988;104(6):1037-1045.
Upp, James R. ; Trudel, Judith L. ; Townsend, Courtney ; Alexander, Robert W. ; Rajaraman, Srinivasan ; Nealon, William H. ; Greeley, George H. ; Thompson, James C. / Establishment of a human gastrinoma in nude mice. In: Surgery. 1988 ; Vol. 104, No. 6. pp. 1037-1045.
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