Stimulation of growth of a colon cancer cell line by gastrin

Kusyk, Christine J.; McNiel, Nancy O.; Johnson, L. R.

doi:10.1152/ajpgi.1986.251.5.g597

Cited by 58 publications

(40 citation statements)

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“…thymidine; no such growth effects were observed with asynchronous cells. Specific culture conditions involving synchronisation of cells with thymidine and growth in serum-free medium have been reported previously to be important in revealing trophic effects of gastrin on gastric and colon cancer cells in vitro (Kusyk et al, 1986;Watson et al, 1988;Guo et al, 1990). In previous studies, ornithine decarboxylase activity, or 3H-thymidine or 75Se-selenomethionine incorporation were used as indices of responsiveness of AR4-2J cells to gastrin (Scemama et al, 1989;Seva et al, 1990;Watson et al, 1991a).…”

Section: Discussionmentioning

confidence: 99%

“…Proglumide, a non-specific gastrin/CCK receptor antagonist, inhibited the growth stimulatory effects of gastrin on mouse colon cancer in vivo and prolonged the survival of tumour-bearing mice (Singh et al, 1987;Beauchamp et al, 1985). Direct trophic effects of gastrin and CCK on gastrointestinal and pancreatic tumour cells in vitro are widely reported (Sirinek et al, 1985;Kusyk et al, 1986;Watson et al, 1988Watson et al, , 1989Imdahl et al, 1989;Guo et al, 1990;Smith et al, 1991). Inhibition of gastrointestinal and pancreatic tumour cell growth by gastrin/CCK receptor antagonists has also been shown by several workers (Hoosein et al, 1988;Imdahl et al, 1989;Guo et al, 1990;Smith et al, 1990a).…”

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confidence: 99%

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Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin

Blackmore

Bh²

1992

Br J Cancer

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Summary The control of cell proliferation by gastrin has been investigated in a rat pancreatic tumour cell line, AR4-2J. Exogenous gastrin, 10-12 to 10-8 M, stimulated cell growth of thymidine-synchronised AR4-2J cells cultured over 48 h in serum-free medium. Cell lysates of AR4-2J cells contained an average of 4.5 and 3.5 pg gastrin per 106 cells, when grown in serum-supplemented or serum-free media, respectively, as revealed by radioimmunoassay. In serum-free medium, AR4-2J secrete 34ngl 10-6 cells of gastrin over 48h. Addition of an anti-gastrin immunoglobulin preparation, but not control immunoglobulins, caused a maximum 52% reduction in cell growth. These data are consistent with an autocrine role for gastrin in the control of AR4-2J cell growth. These results were supported by studies with gastrin/CCK receptor antagonists. Six non-peptide gastrin/CCK receptor antagonists inhibited AR4-2J cell growth in a concentration-related manner. The concentration required for 50% inhibition (IC50) of cell growth by the amino acid-derived antagonists proglumide (3.5 x 10-M), benzotript (1.8 x 10-3 M), loxiglumide (1.1 x 10-4 M) and lorglumide (6.7 x 10-5 M) were of the same order and significantly correlated with their IC50 for inhibition of 1251-gastrin binding to AR4-2J cells. Inhibition of cell growth by these antagonists was partially reversed by the addition of exogenous gastrin. In contrast, the ICm for inhibition of cell growth with two benzodiazepine-derived antagonists, the CCK-B receptor antagonist L-365,260 (4.6 x 10-5 M) and the CCK-A receptor antagonist devazepide (1.7 x 10-' M) were two-three orders of magnitude greater than those required to inhibit gastrin binding (10-8-10-7 M). The growth inhibitory effects of L-365,260 and devazepide were not reversed by exogenous gastrin suggesting these benzodiazepine-derived antagonists do not inhibit cell growth by interaction with gastrin receptors. The results are consistent with gastrin being an autocrine growth factor in AR4-2J cells, and that stimulation of cell growth is due to stimulation of the gastrin, rather than CCK-B, receptor sub-type. This study highlights that gastrin receptor antagonists warrant further investigation as agents to control growth of tumours, such as those from the gastrointestinal tract, which express gastrin receptors.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin

Blackmore

Bh²

1992

Br J Cancer

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“…Each experiment was repeated three times. As a direct measure of DNA replication (Kusyk et al, 1986), 0.1 pCi of methyl-['H]-thymidine (DuPont, NEN, Boston, MA, USA) was added to the wells and incubated for a further 8, 24 and 48 h. The cells were then harvested using a cell harvester (PHD cell harvester, Cambridge Technology, USA) and counted using a beta-counter (Minaxi Tri-carb 4000 series, United Technologies Packard, USA).…”

Section: Methodsmentioning

confidence: 99%

Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth

Lawson

Adams²,

Dl³

1996

Br J Cancer

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Summary Histamine has recently been shown to be a growth factor for some gastric and colorectal cancer cells. Previous studies have shown that cimetidine blocks in vitro and in vivo histamine-stimulated growth and cAMP release from the human colonic cancer cell line, C170. In this study, ranitidine, another H2 receptor antagonist, did not affect either basal or histamine-stimulated in vitro proliferation of C170, and failed to prevent cAMP release in vitro. Ranitidine did not inhibit in vivo growth of C170 at a dose of 1, 10, 25, 50 or 100 mg kg-', in contrast to 50 mg kg -day-' cimetidine, which produced 39.3% inhibition of tumour volume (P<0.01) after 23 days' treatment. Ranitidine did not inhibit in vivo histamine-stimulated growth of C170 cells.LIM2412, another colonic cancer cell line, was significantly stimulated by both cimetidine and ranitidine in vivo. Ranitidine had no effect on in vitro cell proliferation.

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“…However, Lahm et al (15) argue that depending on the differentiation status, one molecule may exert different effects and that the same cell line may even respond in different ways to a single growth factor. Accordingly, although gastrin has been widely shown to stimulate the in vitro growth of colorectal cancers (7,14,24), Weinstock and Baldwin (26) and Kolori et al (13) were unable to demonstrate such a gastrin-induced trophic effect in several GI cell lines.…”

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confidence: 99%

Characterization of the differentiation of human colorectal cancer cell lines by means of Voronoi diagrams

et al. 1993

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This paper describes differentiation in terms of population dynamics through the medium of Voronoi paving which enables (via digital cell image analysis) the structure of human LOVO and HCT-15 colorectal neoplastic cell colonies growing on histological slides to be characterized. Two other tests were also used, i.e., the colorimetric MTT assay that enables the cell growth level to be determined, and a test allowing the assessment of the proliferation index, i.e., the percentage of cells in the S phase of the cell cycle. The results show that these colorectal neoplastic cells exhibited a comparatively high level of organisation in terms of the topographical distribution of nuclei within the clones when the cells were cultivated in media containing even small amounts of fetal calf serum. On the other hand, certain chemically defined media completely overturned this "pseudo-tissular" architecture. Furthermore, the colorectal cells growing in media including fetal calf serum exhibited relatively large and dense clones, undergoing an increase in the density of these clones when hormones were added to the culture medium and, concomitantly, a decrease in their proliferation. In contrast, the cells growing in chemically defined media generally exhibited smaller clones whose cell proliferation was paradoxically greater than that of the cells referred to above. This seems to bring out the importance of the part played by the cell loss factor in this cell population dynamic.

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Stimulation of growth of a colon cancer cell line by gastrin

Cited by 58 publications

References 0 publications

Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin

Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin

Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth

Characterization of the differentiation of human colorectal cancer cell lines by means of Voronoi diagrams

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