Reference SummaryGutierrez LS, Carcinogenesis 2003 Feb;24(2):199-207
Title |
Thrombospondin 1--a regulator of adenoma growth and carcinoma progression in the APC(Min/+) mouse model. | ||||||||
Authors |
Gutierrez LS; Suckow M; Lawler J; Ploplis VA; Castellino FJ | ||||||||
Journal |
Carcinogenesis | ||||||||
Volume |
24 | ||||||||
Issue |
2 | ||||||||
Year |
2003 | ||||||||
Pages |
199-207 | ||||||||
Abstract |
Thrombospondin 1 (TSP-1) is a multifunctional extracellular matrix protein that is an endogenous regulator of tumor angiogenesis. The effects of TSP-1 on adenoma formation and development into cancerous lesions has been evaluated in the Min(/+) (multiple intestinal neoplasia) mouse model. These mice develop multiple adenomas in the small intestine due to a mutation in the homologous APC (adenomatous polyposis coli) gene. As in its human counterpart, these adenomas may progress to carcinomas. Intestines of APC(Min/+) mice were dissected and histologic evaluation of adenomas was then conducted. Significant increases in vascularization and proliferation were observed in adenomatous, as compared with normal, mucosa. TSP-1 immunostaining revealed significant decreases in the number and intensity of positive cells in adenomas, as compared with normal mucosa. TSP-1 scores were inversely correlated with vascularity and proliferation rate. Cross breeding of mice homozygous for a deletion of the TSP-1 gene (TSP-1(-/-)) with mice heterozygous for the APC gene mutation (APC(Min/+)), resulted in animals that showed a significant increase in adenoma number and diameter. Also, histopathological examination of these adenomas showed accelerated dysplasic changes, carcinoma in situ and early invasion, compared with their APC(Min/+) littermates. Moreover, a significant decrease of TUNEL-positive cells was observed in intestinal adenomas of TSP-1(-/-)/APC(Min/+) mice. This study reports the first in vivo impact of TSP-1 during early stages of tumor initiation and development in an intestinal carcinogenesis model and demonstrates that TSP-1 affects both angiogenesis and tumor cell apoptosis. | ||||||||
Links |
J:79641 – MGI References 12584168 – National Library of Medicine/PubMed |
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Strain Notes
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| [not specified]-Thbs1tm1Hyn | Intestine - Small Intestine hyperplasia | Intestine - Small Intestine |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine adenoma | Intestine |
observed |
||
| [not specified]-ApcMin/+ Thbs1tm1Hyn | Intestine adenoma | Intestine |
observed |
||
| [not specified]-ApcMin/+ | Intestine adenoma | Intestine |
observed |
||
| [not specified]-ApcMin/+ Thbs1tm1Hyn | Intestine carcinoma | Intestine |
observed |
||
| [not specified]-ApcMin/+ | Intestine carcinoma | Intestine |
observed |
||
| [not specified]-ApcMin/+ Thbs1tm1Hyn | Mammary gland tumor | Mammary gland |
0 |
||
| [not specified]-ApcMin/+ Thbs1tm1Hyn | Skin tumor | Skin |
0 |
||
| [not specified]-ApcMin/+ Thbs1tm1Hyn | Stomach tumor | Stomach |
0 |