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PMID: 17148680 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Overexpression of heme oxygenase-1 in murine melanoma: increased proliferation and viability of tumor cells, decreased survival of mice.

The American journal of pathology ·Vol. 169 ·No. 6 ·2006-12-00 ·Pages 2181-98

Was H, Cichon T, Smolarczyk R, Rudnicka D, Stopa M, Chevalier C, Leger JJ, Lackowska B, Grochot A, Bojkowska K, Ratajska A, Kieda C, Szala S, Dulak J, Jozkowicz A

Abstract

Heme oxygenase-1 (HO-1), a cytoprotective enzyme, can be induced in tumors in response to anti-cancer therapies. We investigated the role of HO-1 in B16(F10), S91, and Sk-mel188 melanoma cells. Overexpression of HO-1 after transduction with adenoviral vectors increased cell proliferation, resistance to oxidative stress generated by H2O2, and angiogenic potential as determined by induction of endothelial cell divisions. Likewise, cells stably transfected with HO-1 cDNA (B16-HO-1) showed higher proliferation, stress resistance, and angiogenic activity than the wild-type line (B16-WT). HO-1 overexpression in tumors significantly shortened survival of mice after subcutaneous injection of cancer cells (38 and 22 days for B16-WT and B16-HO-1, respectively; P=0.017). This also resulted in development of more packed tumors, with more melanoma cells, and reduced inflammatory edemas. Mice injected with B16-HO-1 had lower levels of tumor necrosis factor and higher serum concentrations of its soluble receptor tumor necrosis factor-RI, whereas tumors overexpressing HO-1 displayed augmented vascularization and stronger production of vascular endothelial growth factor. Finally, B16-HO-1 cells injected intravenously formed more metastases in lungs. Thus, HO-1 overexpression increased viability, proliferation, and angiogenic potential of melanoma cells, augmented metastasis, and decreased survival of tumor-bearing mice, suggesting that induction of HO-1 may be detrimental in anti-cancer therapy of melanoma.

MeSH Terms
Animals Cell Line, Tumor Cell Proliferation Cell Survival Cytokines/metabolism Heme Oxygenase-1/metabolism Humans Lung Neoplasms/secondary Melanoma, Experimental/enzymology,mortality,pathology Mice Neoplasm Metastasis Neovascularization, Pathologic/etiology,metabolism Survival Rate Transfection Vascular Endothelial Growth Factor A/metabolism
Chemicals
Cytokines Vascular Endothelial Growth Factor A Heme Oxygenase-1
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Was Halina
Department of Medical Biotechnology, Faculty of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
Cichon Tomasz
Smolarczyk Ryszard
Rudnicka Dominika
Stopa Magdalena
Chevalier Catherine
Leger Jean J
Lackowska Bozena
Grochot Anna
Bojkowska Karolina
Ratajska Anna
Kieda Claudine
Szala Stanislaw
Dulak Jozef
Jozkowicz Alicja
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2006.051365
Published
2006-12-00
Pages
2181-98
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1762485
Subset
IM
Grants
Wellcome Trust · 073974 · United Kingdom
External Links
PubMed source DOI: 10.2353/ajpath.2006.051365 PMC Full Text View journal details
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