Paper dels factors neuronals sema3f i ntn1 en la transició de càncer de mama in situ a invasiu
- Autores: Núria Moragas Garcia
- Directores de la Tesis: Pedro Gascón Vilaplana (dir. tes.), Gemma Fuster Orellana (codir. tes.)
- Lectura: En la Universitat de Barcelona ( España ) en 2021
- Idioma: español
- Tribunal Calificador de la Tesis: A. Genescà (presid.), M. Carme Auladell i Costa (secret.), Pedro L Fernandez Ruiz (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad de Barcelona
- Materias:
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- Resumen
The most plausible theory about the evolution of breast cancer considers ductal carcinoma in situ (DCIS) as a non-obligated precursor of the invasive phase (IDC), which eventually ends in a metastatic state. DCIS is characterized by the proliferation of mammary epithelial cells confined to breast ductal structures and surrounded by both, the myoepithelial cell layer and by the basement membrane (BM), without invading the extracellular matrix. From the moment invasion occurs it is considered an IDC. It is unknown what triggers the evolution of DCIS and it is not possible to predict which cases will progress rapidly to IDC and which of them will remain stable. Therefore, it is essential to improve our knowledge about these pre-invasive BC lesions to predict the individual risk of progression and to carry out a tailored treatment in each case. In this context, it is noteworthy that the influence of the microenvironment is key in the evolution of DCIS to IDC. This study was designed to focus on neural factors, which have been previously linked to the onset, progression and survival of breast cancer. For this reason, the aim of this thesis has been to decipher the role of two nervous system-related factors, SEMA3F and NTN1, in the transition from DCIS to invasive disease.
On one hand, this thesis shown that SEMA3F is a protumoral element that is synthesized by tumor epithelial cells and promotes the transition from DCIS to IDC at least partially through its coreceptors NRP1 and NRP2. In addition, SEMA3F has a protumorigenic effect on myoepithelial cells, affecting and modifying them towards a tumor-altered phenotype. However, the antitumor role of myoepithelial cells is able to counteract the effects of SEMA3F. On the other hand, NTN1 is shown to inhibit the invasion capacity of epithelial cells in IDC, leading them to a less aggressive tumoral phenotype. In addition, overexpression of NTN1 protects myoepithelial cells against loss of their antitumor function. Finally, evidences are given for the existence of a relationship between these two molecules and their role in DCIS, while overexpression of SEMA3F down-regulates NTN1 expression.
In conclusion, this thesis contributes to a better understanding of DCIS and its possible evolution into invasive pathology, considering the effects of neuronal factors, SEMA3F as a pro-invasive molecule and NTN1 as an element that blocks the progression to invasive breast cancer. This deeper knowledge about BC biology is at the same time a contribution to possible biomarkers of diagnosis and prognosis of DCIS, and also a proposal of new targeted treatment strategies to control breast cancer in the more therapeutically affordable pre-invasive phase.
