Molecular analysis of chemokines and their receptors to assess the metastatic potential in breast cancer cells using cell traps in vitro and in vivo

Breast cancer is the most common malignant neoplasm in women, accounting for 12.5% of new cases of cancer. In Latin America, its incidence is increasing, with high mortality related to invasion and metastasis of the tumor. Although metastasis is a key process, its mechanisms remain poorly understood, and detecting tumor cells with metastatic capacity is a challenge. 2D and 3D cell culture models do not accurately reproduce the properties of primary tumor or metastasis, and patient-derived metastatic tissue samples are often in advanced stages. Only 10% of the circulating tumor cells (CTCs), responsible for initiating metastasis, are able to invade, so it is crucial to understand their mechanisms and characteristics in the early stages of the process.
This project proposes a “cell trap” model, designed to imitate a tissue that attracts and captures the CTCs with metastatic capacity, allowing their subsequent analysis. This tissue includes extracellular matrix and chemokines that mediate cell traffic, seeking to replicate the progression towards metastasis and mechanisms such as inflammation that guide it.
The overall objective of the project is to analyse the molecular profile of chemokines and their receptors in order to assess the metastatic potential in breast cancer cells trapped in cell traps, both in vitro and in vivo.
Specific objectives include: (1) generation of cell traps by bioprinting for in vitro and in vivo experiments, (2) analysis of gene and protein expression of chemokine receptors on CTCs trapped under different inflammatory conditions; and (3) the evaluation of the metastatic potential of these cells in animal models, comparing invasive versus non-invasive cells.

Genetic analyses shall be performed using RNAseq and RT-qPCR, and functional tests shall include migration and invasion testing. Preliminary results suggest that these traps can capture CTCs using chemokines, and the project seeks to standardize the process to provide valuable information on the genetic and protein profiles of invasive CTCs, What could improve understanding of breast cancer and open up new therapeutic pathways.

Participantes :

Julio Valdivia Silva MD, PhD- UTEC

Rafael Tapia Limonchi – UNTRM

Oscar Carnero Fuentes – Auna Valle Sur

María Gloria Soldevila – UNAM

Rodney Macedo – Albert Einstein College