HspBP1 levels are elevated in breast tumor tissue and inversely related to tumor aggressiveness.

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/microg protein, n = 51) compared to normal adjacent tissue (3.17 ng/microg 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 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.

Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors.

Heat shock protein (Hsp)-peptide complexes purified from tumors can prime the immune system against tumor antigens, but how they contribute to the generation of immune responses against naturally occurring tumors is unknown. Murine tumors expressing high amounts of Hsp70 are preferentially rejected by the immune system, suggesting that low Hsp70 expression is advantageous for tumor growth in the host. To determine whether Hsp70 was differentially expressed in human tumors, inducible Hsp70 expression was quantitatively (by Western blot) and qualitatively (by immunohistology) analyzed in 53 biopsies of tumor and normal breast tissue. The mean expression of inducible Hsp70 was significantly higher in tumor compared with normal tissue (U = 899.0; P = 0.0033). However, a significant negative association of the amount of Hsp70 expressed by tumor tissue was found with metastasis (r = -0.309; P = 0.05). After 3 years, follow-up analysis determined that 7 of the 53 patients relapsed, and 5 died. Hsp70 expression in tumor (but not normal) cells was significantly lower in relapse patients and patients with metastatic disease than in patients with no relapse or metastasis. Together, these observations support the hypothesis that Hsp70 plays a role in tumor expansion in vivo, and tumors that downregulate it may be able to evade immunosurveillance and grow.

Importância clínica da angiogênese tumoral no câncer colorretal / Clinical importance of tumor neovascularization in colorectal neoplasms

Sabe-se que diversos fatores estão envolvidos na progressão tumoral. Há um aspecto nesse processo que vem chamando cada vez mais a atenção dos pesquisadores nos últimos anos: a angiogênese(1,2). Atualmente é consenso que a formação de novos vasos pela neoplasia é um fator crucial para o sucesso do crescimento tumoral. A partir disso, tem aumentado o interesse pelo estudo de inibidores da angiogênese como novas armas terapêuticas. O carcinoma colorretal é uma das neoplasias mais estudadas quanto ao potencial angiogênico e o uso de um anticorpo monoclonal contra o fator de crescimento vascular endotelial mostrou aumentar a sobrevida dos pacientes(3)