No abstract

HspBP1 is a co-chaperone that binds to and regulates the chaperone Hsp70 (Hsp70 is used to refer to HSPA1A and HSPA1B). Hsp70 is known to be elevated in breast tumor tissue, therefore the purpose of these studies was to quantify the expression of HspBP1 in primary breast tumors and in serum of these patients with a follow-up analysis after 6 to 7 years. Levels of HspBP1, Hsp70, and anti-HspBP1 antibodies in sera of breast cancer patients and healthy individuals were measured by enzyme-linked immunosorbent assay. Expression of HspBP1 was quantified from biopsies of tumor and normal breast tissue by Western blot analysis. The data obtained were analyzed for association with tumor aggressiveness markers and with patient outcome. The levels of HspBP1 and Hsp70 were significantly higher in sera of patients compared to sera of healthy individuals. HspBP1 antibodies did not differ significantly between groups. HspBP1 levels were significantly higher in tumor (14.46 ng/μg protein, n= 51) compared to normal adjacent tissue (3.17 ng/μg protein, n= 41, p<0.001). Expression of HspBP1 was significantly lower in patients with lymph node metastasis and positive for estrogen receptors. HspBP1 levels were also significantly -008-0085-6 This work was supported by FAPERGS, CNPq, and the National Institute of General Medical Sciences grant number GM072628-02 (V.G.)Cell Stress and Chaperones (2009) 14:301-310 DOI 10.1007/s12192The expression of HspBP1 (an Hsp70 co-chaperone) was analyzed in tumor samples and sera from breast cancer patients. HspBP1 is over expressed in these tumors and a seven year follow-up analysis found an association with a poor prognosis. Chaperones have been shown to play important roles in tumor biology and immunology; therefore, we believe the data in this study will serve as a basis for the formulation of a new hypothesis on chaperone-co-chaperone interactions and their role in tumor growth. lower in patients with a higher incidence of metastasis and death following a 6 to 7-year follow-up. The HspBP1/Hsp70 molar ratio was not associated with the prognostic markers analyzed. Our results indicate that low HspBP1 expression could be a candidate tumor aggressiveness marker.

The tumor microenvironment shelters a complex network of mechanisms that enables local Immunosuppression to support tumor growth. In this study we found that, B16F10 melanoma growth is inversely correlated with peritumoral infiltrate cell number and with cell numbers in draining lymph nodes. Tumor growth ensued even when a foreign antigen was expressed by B16F10 cells in the presence of naïve specific CD8 + T cells. Treatment with TLR agonists has shown to sometimes result in tumor regression, however, not always with long-lasting effects. We compared the relevance of different injection regimens of lipopolysaccharide (LPS). Tumor growth was arrested only by intratumoral LPS injection after the tumor was already established. This result was accompanied by a dramatic change in DC activation inside the tumor. Intratumoral LPS also enhanced antigen presentation and tumor-specific CD4 + T cell production of IFN-γ. Injection of LPS before tumor challenge or codelivery of tumor cells and LPS did not have any effect on tumor progression. Our results suggest that an efficient antitumor immune response leading to tumor regression can be achieved with proper TLR4 activation inside the tumor tissue, impacting the tumor microenvironment. These findings are relevant for the design of treatment for patients with malignant melanomas.