Laia Puig Blasco

Name: Laia Puig Blasco

Nationality: Spanish

Academic Background: B.Sc. in Biotechnology, Universitat Autònoma de Barcelona, Spain; M.Sc. in Biomedicine, Lund University, Sweden

Project Title: Deciphering the role of ADAM proteases in the crosstalk between cancer cells and non-malignant cells in the tumor microenvironment

Project Background: Tumors are commonly perceived as rapidly proliferating cancer cells that have the potential to spread throughout the body. However, tumors not only consist of malignant cancer cells, there are also healthy cells within the tumor mass, such as the cells of the immune system. Immune cells initially attempt to eliminate unhealthy or damaged cells, but this elimination is not always successful in the tumor setting. Cancer cells can hijack the immune system to, instead of being destroyed, escape from its attack and support their growth.

Cancer cells can only influence other cells present in the tumor if there is a constant communication between them. These interactions can happen through direct cell-cell contact or via soluble factors that are released into the tumor environment and target a specific cell type. Interestingly, one of the cancer cells’ strategies to release these substrates is to make use of their “ADAM-weapons”. ADAMs (a disintegrin and metalloproteinase) are scissor-like proteins expressed on the cell surface with the ability to cleave other proteins and release them into the surrounding tumor environment. Cancer cells exploit their “ADAM-weapons” during tumor progression by cleaving substrates that enhance their proliferation, invasion and metastasis.

Nevertheless, we believe that cancer cells make much greater use of their “ADAM-weapons”, especially when it comes to remodeling their surrounding environment. We hypothesize that ADAMs play a key role in the crosstalk between cancer cells and non-malignant cells by shedding substrates that shape the tumor microenvironment towards a tumor-promoting setting. Therefore, if we understand how cancer cells use their “ADAM-weapons” to communicate with non-malignant cells and alter the surrounding environment to their benefit, we could provide some better tools to fight cancer.

Project Aim: The aim of this PhD project is to understand how ADAMs, expressed in cancer cells, influence the different cell populations in the tumor microenvironment (TME) and subsequently affect cancer progression. We are interested in performing a comparative study including several ADAMs and investigating their specific role in the crosstalk between cancer cells and non-malignant cells in the TME. Accordingly, we will approach this project using an in vivo screening strategy based on a generated ADAM-knockout library of murine cancer cells and profiling the tumors by flow cytometry. Based on the results, we will focus on a specific ADAM and further investigate the way it shapes the TME.

Expected Outcome:  This research project will provide new mechanistic insight on the ADAM-dependent remodeling of the TME during cancer progression. We will reveal how different ADAMs, with similar structure and even overlapping substrates, influence the tumor and its surroundings in their specific way. This knowledge will contribute to the discovery of potential cancer targets and the development of better therapeutic strategies for cancer treatment.

Contact:  laia.blasco@bric.ku.dk