Universitat de Barcelona
Casanovas i Casanovas, Oriol
Viñals Canals, Francesc
2020-12-09
217 p.
Universitat de Barcelona. Facultat de Medicina
[eng] The arrival of antiangiogenic therapies represented a huge advance in the treatment of different tumors, such as renal carcinoma. However, despite initial good results, some tumors were able to develop different mechanisms to adapt to the new conditions and continue growing. Thus, resistance to the antiangiogenic drugs appeared. Moreover, preclinical studies showed that some tumors increased their invasive and metastatic capacity after the therapy. Different murine orthoxenografts models, derived from patients with renal carcinoma, were developed to characterize the response to the antiangiogenic treatment. Both drugs used, DC101 and Bevacizumab, produced a reduction of the tumor growth and its volume, as well as a reduction of the number of vessels. However, when tumor invasion was evaluated, it could be observed that not all tumor models responded equally. While some tumors showed a higher metastatic capacity and an increase in invasiveness and aggressiveness after the treatment, others did not show any alteration of their characteristics. To study the mechanisms involved in the increase of tumor malignization, different assays comparing the gene expression of non-invasive and pro-invasive tumors after the antiangiogenic treatment were developed. These analyses generated a list of candidate genes that could be responsible for the invasive process, with CD44 among them. In this thesis, we have studied the role of CD44 in the tumor invasion and migration processes using in vitro and in vivo models of renal carcinoma. We have explored the signaling pathway that could be induced due to the CD44 activation. The Src signaling route was possibly shown to be involved in the invasive process of cancer cells. The mechanism responsible for CD44 activation has also been investigated. Between different candidates, Serglycin appeared as a possible ligand and inducer of CD44. Thus, this thesis opens different study ways to determine the molecules responsible for tumor invasion after antiangiogenic treatment and develop new different strategies to overcome the resistance.
Oncologia; Oncología; Oncology; Cultiu cel·lular; Cultivo celular; Cell culture; Biologia molecular; Biología molecular; Molecular biology; Anàlisi de medicaments; Análisis de medicamentos; Drugs analysis; Càncer de fetge; Càncer de hígado; Liver cancer
577 - Material bases of life. Biochemistry. Molecular biology. Biophysics
Ciències de la Salut
Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Investigació Biomèdica de Bellvitge (IDIBELL) i a l'Institut Català d'Oncologia (ICO)
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Facultat de Medicina [457]
