Contribuições para o estudo da heterogeneidade inter e intratumoral em neoplasias mamárias em cadelas

Abstract

CORDEIRO, Y.G. Contribution to the study of inter and intratumor heterogeneity in canine mammary carcinomas. 2020. 99f. PhD Thesis. Faculdade de Zootecnia e Engenharia de Alimentos. Universidade de São Paulo. 2020.Mammary tumors are among the most common types of cancer in dogs as well as in humans.Considered as excellent models for the study of cancer biology, similarities such as their spontaneous nature are difficult to be replicated in other animal models. Mammary tumors can be classified in many tumor subtypes, presenting a higher degree of inter and intratumoral heterogeneity. New insights on biomolecular mechanisms may lead to new therapeutic targets, improving diagnosis and prognosis and also improving patient care. Therefore, the main purposes of this work were: (i) To correlate global gene expression with tumorigenicity and invasion potential in canine mammary carcinoma cell lines, in order to establish an in vitro model for basic and applied oncology studies; and (ii) To characterize, using image mass spectrometry (MALDI-MSI), tumor subpopulations in primary tissues and metastasis through morphological and molecular features, in order to identify altered cancer-related pathways. In the first chapter, we showed differences regarding gene expression between two cell lines and a normal mammary gland tissue, as well as a higher invasion and in vivo tumorigenic potential of M25 cells associated to upregulation of genes involved in focal adhesion and extracellular matrix organization. In chapters 2 and 3, alterations in protein expression profiles of tumor and metastatic subpopulations were identified using both the morphological and the molecular phenotype of microscopically indistinguishable populations. Such differences were found mainly related to protein-processing pathways, extracellular matrix components, cell adhesion pathways and epigenetic regulations. These results should direct a search for the determination of biomarkers of populations in distinct levels of tumor progression.