Investigation of the effects of immunization with recombinant heat shock-90 protein on molecular methods in a breast cancer model

Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related mortality among women. The development and progression of this disease result from complex interactions between genetic and environmental factors. During these processes, chaperone proteins, which play critical roles in cellular stress responses, are essential for the survival and proliferation of cancer cells. Heat Shock Protein 90 (HSP90) is one of these chaperone proteins, responsible for protein folding, stabilization, and degradation within the cell. In addition to its role in normal cellular processes, HSP90 is overexpressed in cancer cells, contributing significantly to tumor development and progression. Therefore, the inhibition and targeting of HSP90 is considered a promising new strategy in cancer therapy. This study aims to investigate the protective and therapeutic effects of immunization with recombinant HSP90 against breast cancer in a mouse model of triple-negative breast cancer. A total of 80 female BALB/c mice were used in this study. Eight groups (n=10) were established: 0.5 μg HSP90 group, 1 μg HSP90 group, control group, tumor group, 0.5 μg HSP90 prophylactic group, 1 μg HSP90 prophylactic group, 0.5 μg HSP90 therapeutic group, and 1 μg HSP90 therapeutic group. The prophylactic groups received HSP90 once a week for 4 weeks, starting 28 days before tumor inoculation. The therapeutic groups received subcutaneous HSP90 simultaneously with tumor injection, followed by once-weekly injections for 4 weeks. The control group received no treatment, while the tumor group received tumor cell injection and simultaneous subcutaneous saline injections along with HSP90 injections. The experimental phase concluded on the 29th day after tumor inoculation. Tumor tissues were collected from the mice. Tumor masses were examined macroscopically, and tumor weights, dimensions, and volumes were determined. Samples were taken for histopathological, immunohistochemical, and real-time polymerase chain reaction analyses. Macroscopically, primary tumors ranged from 0.5 to 2 cm in diameter, with shapes varying from oval to cylindrical. In the 0.5 μg HSP90 prophylactic group, primary tumor volume, primary tumor weight, and PCNA expression were reduced. Decreased Ki-67 expression was noted in both therapeutic and prophylactic groups. CD31 and HSP90 expressions were reduced in the therapeutic groups. The findings suggest that therapeutic and prophylactic immunization with recombinant HSP90 can reduce breast tumor proliferation, angiogenesis, and metastasis in a breast cancer model, demonstrating significant antitumor effects. These results indicate that HSP90 may be used as a potential immunotherapeutic agent in breast cancer treatment, potentially improving prognosis and increasing survival rates.