Qiaoxia Wang

HSP72 and gp96 in gastroenterological cancers

Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of gastrointestinal carcinomas but detailed mechanisms are still ambiguous. Human esophageal cancer, gastric cancer, colon cancer and liver cancer are common gastrointestinal malignant carcinomas in the world. The studies indicated that there existed a significant correlation between the expression of HSP72, gp96 and the development and progression of digestive carcinomas. HSP72 and gp96 expression were significantly associated with the presence of tumor infiltration, lymph node and remote metastasis. Interestingly, studies have found that HSP72 chaperoned alpha-fetoprotein (AFP), HBx in hepatocellular carcinoma, and CD44 in colonic carcinomas. The further researches demonstrated that HSP72-AFP or gp96-AFP recombined vaccine could elicit specific anti-tumor immunity. The high-level expression of HSP72 and gp96 may be not only used as diagnostic or prognostic markers for gastrointestinal carcinomas but also as better immunotherapeutic vaccines in the cancers.

Specific Antitumor Immunity Induced by Cross-linking Complex Heat Shock Protein 72 and Alpha-fetoprotein

Hepatocellular carcinoma (HCC) is one of the most common malignancies over the world. Alpha-fetoprotein (AFP) is an oncofetal protein during HCC development that could generate weaker and less reproducible antitumor protection, and it may serve as a target for immunotherapy. Therefore, it is imperative to enhance its immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing tumors. In this study, by way of glutaraldehyde cross-linking, we constructed a potential therapeutic protein complex vaccine, heat shock protein 72 (HSP72)/AFP. Our results demonstrated that AFP and HSP72 synergistically exhibited significant increases in AFP-specific CD8(+) T cell responses and impressive antitumor effects against AFP-expressing tumors. Priming mice with the reconstructed vaccine, we elicited robust strong protective immunity. Our study suggests that a tumor vaccine by cross-linking tumor antigen and HSP72 is a promising approach for cancer therapy.

Glycoprotein 96 and α-Fetoprotein Cross-Linking Complexes Elicited Specific Antitumor Immunity

Hepatocellular carcinoma (HCC) is one of the most common malignant gastroenterological cancers over the world. α-fetoprotein (AFP) is an oncofetal protein produced during HCC development that could generate weaker and less reproducible antitumor protection, and it may serve as a target for immunotherapy. Therefore, it is imperative to enhance its immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing tumors. In this study, by way of glutaraldehyde cross-linking, we constructed a potential therapeutic protein vaccine, glycoprotein 96 (gp96)/AFP. Our results demonstrated that AFP and gp96 synergistically exhibited significant increase in AFP-specific CD8⁺ T-cell responses and impressive cytotoxic antitumor effect against AFP-expressing tumors. Priming mice with the reconstructed vaccine, we elicited robust strong protective immunity. Our study suggests that tumor vaccine by cross-linking tumor antigen and gp96 is a promising approach to cancer therapy.

Interaction between Heat Shock Protein 72 and CD44v6 in Human Colonic adenocarcinoma

Abstract-Background: CD44v6 is a splice variant of CD44 (CD44v) could probably promote cancer cells to adhere to vascular endothelium and base membranes and enhancing the invasion and metastasis of colonic carcinomas. Heat shock protein 72 (HSP72) as a molecular chaperone has been confirmed to overexpress in epithelial carcinoma cells. There may be a possible correlation between the expression of HSP72 and CD44v6 during the growth and differentiation of colonic carcinoma cells. The purpose of the study was to investigate the interaction between heat shock protein 72 and CD44v6 in human colonic carcinomas. Material/Methods: The localization of HSP72 and CD44v6 in human colonic carcinomas were determined by immunohistochemistry and confocal laser microscopy. The interaction between HSP72 and CD44v6 in colonic carcinoma cells was analyzed by immunoprecipitation and Western immunoblots. Results: Colonic carcinoma synchronously co-expressed higher level of HSP72 and CD44v6 than in adjacent normal colonic tissues. HSP72 were stained in cell cytoplasm, while CD44v6 mainly stained in cell plasma and membrane respectively. Based on Western blotting methods, CD44v6 was detected in the immunoprecipitate of anti-HSP72 monoclonal antibody (mAb), while HSP72 existed in the immunoprecipitate of anti-CD44v6 mAb. Conclusions: HSP72 and CD44v6 expression are higher in colonic carcinoma tissues. HSP72 was associated with CD44v6 in human colonic carcinoma cells. The interaction between HSP72 and CD44v6 in human colonic carcinoma cells can be a new route for studying the pathogenesis and immunotherapy of colonic carcinoma.

Co-localization of heat shock protein 72 and CD44v6 in human colonic adenocarcinoma

Background: CD44v6 is a splice variant of CD44 (CD44v) could probably promote cancer cells to adhere to vascular endothelium and base membranes and enhancing the invasion and metastasis of colonic carcinomas. Heat shock protein 72 (HSP72) as a molecular chaperone has been confirmed to overexpress in epithelial carcinoma cells. There may be a possible correlation between the expression of HSP72 and CD44v6 during the growth and differentiation of colonic carcinoma cells. The purpose of the study was to investigate the interaction between heat shock protein 72 and CD44v6 in human colonic carcinomas. Material/Methods: The localization of HSP72 and CD44v6 in human colonic carcinomas was determined by immunohistochemistry and confocal laser microscopy. The interaction between HSP72 and CD44v6 in colonic carcinoma cells was analyzed by immunoprecipitation and Western immunoblots. Results: Colonic carcinoma synchronously co-expressed higher level of HSP72 and CD44v6 than in adjacent normal colonic tissues. HSP72 were stained in cell cytoplasm, while CD44v6 mainly stained in cell plasma and membrane respectively. Based on Western blotting methods, CD44v6 was detected in the immunoprecipitate of anti-HSP72 monoclonal antibody (mAb), while HSP72 existed in the immunoprecipitate of anti-CD44v6 mAb. Conclusions: HSP72 and CD44v6 expression are higher in colonic carcinoma tissues. HSP72 was associated with CD44v6 in human colonic carcinoma cells. The interaction between HSP72 and CD44v6 in human colonic carcinoma cells can be a new route for studying the pathogenesis and immunotherapy of colonic carcinoma

Antitumor Immunity Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific cytotoxic T lymphocyte (CTL) response and its protective effect against AFP-producing tumor. A recombinant vaccine was constructed by conjugating mouse heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-gamma in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-gamma and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50 plusmn 11.70 IFN-gamma spots/10 6 cells vs 41.60 plusmn 10.40 IFN-gamma spots/10 6 cells, 7.32 plusmn 3.14 IFN-gamma spots/10 6 cells, P 3 vs 392.23 plusmn 12.46 mm 3 , 838.63 plusmn 13.84 mm 3 , P<0.01). The study further confirmed the function of heat shock protein 70s immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for HCC.