Where Ideas Grow

Cancer Metastasis

ABOUT

Metastases account for more than 90% of cancer-related deaths. Understanding the biology of therapy-resistant metastatic clones is critical for the development of effective strategies to improve cancer patients’ survival.

The long-term goal of the Cancer Metastasis group is to study the molecular mechanisms underlying the metastatic cascade, focusing on the biological advantage given by cell adhesion to cancer cells, namely for their systemic dissemination, therapy resistance and homing in a distinct microenvironment.

 

RESEARCH

Cancer metastasis involve a series of sequential steps: i) epithelial-to-mesenchymal transition (EMT) of individual cells within the primary tumor leading to their intravasation, ii) systemic survival of such circulating tumor cells (CTCs) and, finally, iii) their ability for extravasation at distant sites, where mesenchymal-to-epithelial transition (MET) potentiates their proliferation into metastatic lesions. Historically, EMT has been shown to be crucial for invasive and circulating cancer cells.
However, it has been recently debated whether it plays actually a role for metastatic establishment. In fact, there are reports proposing that metastasis can directly derive from tumor-derived epithelial micro-emboli that break off from primary tumors, lodging into distal capillaries, where they initiate metastatic growth. These observations are exposing the cancer research community to a novel perspective concerning the metastatic process, in which patients with epithelial cancers may have CTCs retaining adhesion that are able to achieve distant colonization.
Accordingly, our own results and expertise led us to assume that proficient cell-cell adhesion is decisive to promote collective cell invasion, as well as survival of matrix-detached cancer cells, by inducing stem-like properties and by decreasing their oxidative stress, which will potentiate the success of the metastatic process. It is then the aim of the Cancer Metastasis group to understand how cell adhesion is involved in epithelial cancer metastasis, contributing towards the identification of new strategies to monitor this complex biological process and to hamper cell adhesion-mediated survival in metastatic cancer cells, as well as its associated molecular mechanisms.

Using breast cancer as the main model of study, we are focusing our activity to answer the following questions:

  • How do alterations in cell adhesion during early EMT impact cell plasticity, invasive capacity and metastatic spreading?
  • How does cell adhesion, and its induced-signaling pathways, contribute to the invasion-metastasis cascade?
  • How do cancer cell clusters communicate with the metastatic microenvironment and how does this dynamic crosstalk coordinate and dictate colonization capacity?
“Activating invasion and metastasis” is one of the most important hallmarks of cancer; invasion and systemic dissemination, as single cells or as cancer cell clusters, remain the central features to be impaired to prevent cancer metastasis (HE staining of an invasive ductal carcinoma of the breast,

Team

Ongoing Projects

Exossomas radiomarcados: uma ferramenta nanoteranóstica para micrometástases pulmonares no osteossarcoma
Reference: PTDC/BTM-SAL/4451/2020
Proponent: Universidade de Coimbra
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 29-MAR-21 to 28-MAR-24
Explorar o impacto da P-cadeRINa nos Carcinomas sEroSoS de alto grau do ovário sem alterações da reparação homóloga
Reference: BOLSAS NIJE SPO 2021 - PRINCESS
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Sociedade Portuguesa de Oncologia - SPO
From 01-JUL-22 to 30-JUN-24
The clinical impact of VGF as a predictive and prognostic biomarker for breast cancer brain metastasis
Reference: Hologic Women?s Health Award - (CAF): 4271
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Hologic Iberia, SL
From 01-SEP-23 to 31-AUG-25
The impact of triple negative breast cancer secreted extracellular vesicles in bone pre-metastatic reprogramming
Reference: Premio FAZ Ciencia 2023
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Fundação AstraZeneca
From 01-FEB-24 to 31-JAN-26