Breast cancer is the leading cause of cancer death among African American and Hispanic women. Globally, it is the most common and accounts for 12.5% of all new annual cancer cases worldwide, with invasion and metastasis leading to death.

Due to the absence of non-animal models that can improve understanding of the progression of this tumor, 3D bioprinting of breast cancer cell spheroids will be used to generate microtumors that have, potentially, characteristics similar to the original, leading to an analysis of the expression profile of molecules that increase their invasion and metastasis capabilities in vitro and in vivo. Using cell lines and biopsies, tissue bioprinting protocols will be used to generate microtumours that will first be analyzed at the transcriptional level using RNAseq and real-time PCR, focused on chemokines that are guide molecules in cell transport. Cytometry and immunofluorescence will be analyzed to evaluate the greater or lesser expression of the protein. Migration and invasion tests shall be carried out to verify whether these proteins are functional in these cells. Finally, in the in vivo models, the correlation of in vitro findings and histological analysis of major organs commonly metastasized by this cancer will be seen.

The general objective, therefore, is to determine the molecular profile of invasiveness and metastasis of the 3D organoid model of in vitro and in vivo breast cancer.

To do this we will 1): develop 3D organoid cultures of breast cancer tumor lines and primary cultures, 2) compare the genetic expression of chemokines and their receptors under different conditions of inflammatory stimuli in 3D organoids in vitro, 3) evaluate the expression of chemokines and their receptors in the 3D organoid by comparing their expression under different conditions, 4) analyze the compartmentalization of chemokines and their receptors in the 3D organoid and 5) determine functional activity (invasion and metastasis) of chemokine receptors in in vivo models implanted with 3D spheroids.

The expected results are:

1. Optimising 3D models of breast cancer

2. Generating an invasive molecular profile and metastases based on chemokines and their receptors

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3. Suggest mechanisms that may serve as interesting future targets for biological cancer therapy.

This project seeks to generate greater knowledge in the biology of breast cancer that helps understand the mechanisms of invasion and progression of the tumor, and in this way, using a non-animal model lead to the design of new therapeutic strategies.

Researchers:

Julio Ernesto Valdivia Silva – Principal Research
Rodney Jose Mauricio Macedo Gonzales – Co- investigator
Oscar Felipe Carnero Fuentes – Co- investigator
Maria Gloria Soldevilla Melgarejo – Co- investigator
Alonso Rafael Tapia Limonchi – Co- investigator
Stella Maris Chenet Carrasco – Co- investigator

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