Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer

Preparations of stress protein gp96 from tumor cells are active as tumor va ccines by eliciting immune responses against mixtures of individual tumor p eptide antigens which are complexed to gp96. Due to the individual antigeni city of tumors, a vaccine consisting of tumor-derived gp96 has to be prepar ed individually for each patient from autologous tumor tissue. So far, gp96 expression by human tumors has not been analyzed. Here, we report stable a nd mostly homogenous expression of gp96 by colorectal cancer, which was enh anced compared to surrounding tumor stroma in 70% to 80% of colorectal canc er specimens. Fewer non-metastatic than metastatic primary cancer specimens showed enhanced gp96 expression. Glucose deprivation increased gp96 protei n and RNA expression in the human colon cancer cell line HT-29 in accordanc e with the role of gp96 as a glucose-regulated stress protein, Additionally , TNF-alpha, interferons and other cytokines induced an increase of gp96 RN A expression in HT-29 cells, suggesting that gp96 expression by colorectal cancer cells can be influenced by different methods of immunomodulation, Th e stable and homogenous expression of gp96 in 19 primary and metastatic col orectal cancer specimens and the up-regulation of gp96 in colon cancer cell s by glucose deprivation point to an essential role of this stress protein in colorectal cancer, presumably by protecting against hostile conditions o f the tumor micro-environment like glucose deprivation. In view of these re sults, loss of gp96 expression by colorectal cancer cells as an immune esca pe mechanism is unlikely. Int. J. Cancer 86:489-493, 2000, (C) 2000 Wiley-L iss, Inc.