Host acid sphingomyelinase regulates microvascular function not tumor immunity Journal Article
| Authors: | Garcia-Barros, M.; Lacorazza, H. D.; Petrie, H.; Haimovitz-Friedman, A.; Nimer, S.; Fuks, Z.; Kolesnick, R.; Cordon-Cardo, C. |
| Article Title: | Host acid sphingomyelinase regulates microvascular function not tumor immunity |
| Abstract: | Previous studies provided evidence that MCA/129 fibrosarcomas and B16 melanomas grow 2- to 4-fold faster in acid sphingomyelinase (asmase) - deficient mice than in asmase+/+ littermates and are resistant to single-dose irradiation due to inability to mount an apoptotic response in tumor microvascular endothelium. However, others postulated the differences might be associated with a host antitumor immune response in asmase+/+ mice that is not expressed in asmase-/- mice due to phenotypic deficiency in antitumor immunity. The present studies demonstrate that none of the tumor-host combinations displayed the classic criteria of an immunogenic tumor because they lacked endotumoral or peritumoral infiltrates almost entirely. Furthermore, neither MCA/129 fibrosarcoma nor B16 melanoma tumors showed differences in growth or radioresponsiveness when implanted into mutant mouse models (Rag-/- and MEF-/-) lacking functional immune cell [natural killer (NK), NK-T, T, and B cells] populations. Additionally, development and function of B-, T-, and NK-cell populations in asmase -/- mice were normal, indistinguishable from their wild-type littermates. These data provide definitive evidence that MCA/129 fibrosarcomas and B16F1 melanomas do not elicit a host immune response in wild-type mice and that the asmase-/- phenotype is not deficient in antitumor immunity, supporting the notion that the patterns of tumors growth and radiation response are conditionally linked to the ability of the tumor endothelium to undergo ASMase-mediated apoptosis. |
| Keywords: | controlled study; nonhuman; flow cytometry; animal cell; mouse; mouse mutant; animals; mice; mice, knockout; animal tissue; cell infiltration; animal experiment; animal model; mice, inbred icr; enzyme regulation; immune response; fibrosarcoma; melanoma b16; melanoma, experimental; natural killer cell; tumor immunity; tumor growth; microvasculature; sphingomyelin phosphodiesterase; cancer transplantation; immunity, cellular; capillaries; species comparison; male; female; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 64 |
| Issue: | 22 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-11-15 |
| Start Page: | 8285 |
| End Page: | 8291 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-04-2715 |
| PROVIDER: | scopus |
| PUBMED: | 15548696 |
| DOI/URL: | |
| Notes: | Cancer Res. -- Cited By (since 1996):17 -- Export Date: 16 June 2014 -- CODEN: CNREA -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work