7184

HSP90B1

ECGP|GP96|GRP94|HEL-S-125m|HEL35|TRA1;heat shock protein 90kDa beta (Grp94), member 1;HSP90B1;heat shock protein 90kDa beta (Grp94), member 1

94 kDa glucose-regulated protein|endoplasmin|endothelial cell (HBMEC) glycoprotein|epididymis luminal protein 35|epididymis secretory sperm binding protein Li 125m|heat shock protein 90 kDa beta member 1|stress-inducible tumor rejection antigen gp96|tumor

12q24.2-q24.3

protein-coding

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.