Host cyclooxygenase-2 modulates carcinoma growth

Christopher S. Williams, Masahiko Tsujii, Jeff Reese, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticle

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Abstract

Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for rolorectal cancer, but its precise role in carcinogenesis remains unclear. We evaluated the contribution of host-derived COX-1 and COX-2 in tumor growth using both genetic and pharmacological approaches. Lewis lung carcinoma (LLC) cells grow rapidly as solid tumors when implanted in C57BL/6 mice. We found that tumor growth was markedly attenuated in COX-2(-/-), but not COX-1(-/-) or wild-type mice. Treatment of wild-type C57BL/6 mice bearing LLC tumors with a selective COX-2 inhibitor also reduced tumor growth. A decrease in vascular density was observed in tumors grown in COX-2(-/-) mice when compared with those in wild-type mice. Because COX-2 is expressed in stromal fibroblasts of human and rodent rolorectal carcinomas, we evaluated COX-2(-/-) mouse fibroblasts and found a 94% reduction in their ability to produce the proangiogenic factor, VEGF. Additionally, treatment of wild-type mouse fibroblasts with a selective COX-2 inhibitor reduced VEGF production by 92%.

Original languageEnglish (US)
Pages (from-to)1589-1594
Number of pages6
JournalJournal of Clinical Investigation
Volume105
Issue number11
StatePublished - Jun 2000
Externally publishedYes

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Cyclooxygenase 2
Carcinoma
Growth
Neoplasms
Lewis Lung Carcinoma
Fibroblasts
Cyclooxygenase 2 Inhibitors
Inbred C57BL Mouse
Vascular Endothelial Growth Factor A
Rodentia
Carcinogens
Blood Vessels
Carcinogenesis
Pharmacology

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Williams, C. S., Tsujii, M., Reese, J., Dey, S. K., & DuBois, R. N. (2000). Host cyclooxygenase-2 modulates carcinoma growth. Journal of Clinical Investigation, 105(11), 1589-1594.

Host cyclooxygenase-2 modulates carcinoma growth. / Williams, Christopher S.; Tsujii, Masahiko; Reese, Jeff; Dey, Sudhansu K.; DuBois, Raymond N.

In: Journal of Clinical Investigation, Vol. 105, No. 11, 06.2000, p. 1589-1594.

Research output: Contribution to journalArticle

Williams, CS, Tsujii, M, Reese, J, Dey, SK & DuBois, RN 2000, 'Host cyclooxygenase-2 modulates carcinoma growth', Journal of Clinical Investigation, vol. 105, no. 11, pp. 1589-1594.
Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN. Host cyclooxygenase-2 modulates carcinoma growth. Journal of Clinical Investigation. 2000 Jun;105(11):1589-1594.
Williams, Christopher S. ; Tsujii, Masahiko ; Reese, Jeff ; Dey, Sudhansu K. ; DuBois, Raymond N. / Host cyclooxygenase-2 modulates carcinoma growth. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 11. pp. 1589-1594.
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