Avaliação in vivo do potencial antitumoral da co-chaperona HspBP1

Abstract

HSP70 binding protein-1 (HspBP1) is a cochaperone of HSP70. Its classified as a nucleotide exchange factor capable to inhibit or stimulate the ATPase activity of HSP70 thus, regulating its activity. HSP70 have a high expression in several types of tumors, finding present in the plasma membrane of this cells. Thus, HSP70 is considered a tumor biomarker and one way to modulate it activity is by using it cochaperones. The present work aims to evaluate the antitumor capacity of the HspBP1 in two tumor models and to evaluate changes in the profile of the immune system. Here we describe the methods of cloning, expression, purification and obtaining of the HspBP1 and its peptide 1-136. Analyzes by mass spectrometry and determination of the oligomeric state of the protein are also presented. A bioassay was performed to evaluate the presence of endotoxins in proteins. Analysis of the antitumor effect of HspBP1 and peptide 1-136 on melanoma and breast cancer models shows a reduction in tumor volume. The immunological cell phenotypes of the tumor infiltrate and the draining lymph node, by flow cytometry, showed a modulation in response to treatment. In short, our research reveals the ability of HspBP1 to induce a reduction in tumor volume and to modulate the adaptive immune system. Knowledge of HspBP1 ability to modulate the immune system will be useful in assessing this as a possible new antineoplastic drug.