GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression.
Published
Journal Article
In chemical carcinogenesis models, GRP94 (gp96) elicits tumor-specific protective immunity. The tumor specificity of this response is thought to reflect immune responses to GRP94-bound peptide antigens, the cohort of which uniquely identifies the GRP94 tissue of origin. In this study, we examined the apparent tissue restriction of GRP94-elicited protective immunity in a 4T1 mammary carcinoma model. We report that the vaccination of BALB/c mice with irradiated fibroblasts expressing a secretory form of GRP94 markedly suppressed 4T1 tumor growth and metastasis. In addition, vaccination with irradiated cells secreting the GRP94 NH(2)-terminal geldanamycin-binding domain (NTD), a region lacking canonical peptide-binding motifs, yielded a similar suppression of tumor growth and metastatic progression. Conditioned media from cultures of GRP94 or GRP94 NTD-secreting fibroblasts elicited the up-regulation of major histocompatibility complex class II and CD86 in dendritic cell cultures, consistent with a natural adjuvant function for GRP94 and the GRP94 NTD. Based on these findings, we propose that GRP94-elicited tumor suppression can occur independent of the GRP94 tissue of origin and suggest a primary role for GRP4 natural adjuvant function in antitumor immune responses.
Full Text
Duke Authors
Cited Authors
- Baker-LePain, JC; Sarzotti, M; Fields, TA; Li, C-Y; Nicchitta, CV
Published Date
- December 2, 2002
Published In
Volume / Issue
- 196 / 11
Start / End Page
- 1447 - 1459
PubMed ID
- 12461080
Pubmed Central ID
- 12461080
International Standard Serial Number (ISSN)
- 0022-1007
Digital Object Identifier (DOI)
- 10.1084/jem.20020436
Language
- eng
Conference Location
- United States