AUTHOR=Pelosi Andrea Corazzi , Silva Alex Ap. Rosini , Fernandes Anna Maria Alves Piloto , Scariot Pedro Paulo Menezes , Oliveira Manoela Stahl Parisotto , Porcari Andreia M. , Priolli Denise Gonçalves , Messias Leonardo Henrique Dalcheco 

TITLE=Metabolomics of 3D cell co-culture reveals alterations in energy metabolism at the cross-talk of colorectal cancer-adipocytes

JOURNAL=Frontiers in Medicine

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1436866

DOI=10.3389/fmed.2024.1436866

ISSN=2296-858X

ABSTRACT=Colorectum cancer (CRC) is the third most incident and the second most lethal malignant tumor. Despite the recognized association between obesity and CRC, further clarifications are necessary regarding the lipids that are overexpressed when the CRC takes place. In this scenario, the association between metabolomics and a 3D co-culture model involving CRC tumor cells and lipids can enhance the knowledge of energy metabolism modifications at the cross-talk between colorectal cancer and adipocytes. This study aimed to screen potential hydrophilic molecules in the three-dimensional (3D) co-culture of CRC and adipocytes, investigating the metabolome composition of this co-culture released to the extracellular space, the secretome. Pre-adipocytes cells (3T3-L1), human colon carcinoma (HT-29), and the 3D co-culture (3T3-L1 + HT-29) were cultured for the secretome obtention. Then, ultra high-performance liquid-chromatography coupled with high-resolution mass spectrometry were used for metabolomics analysis of each secretome. Overall, 3731 molecules were detected regardless of the cell culture. When comparing the three cultures, 105 molecules presented statistically different abundances between the groups. Among these, 16 were identified, with emphasis to six lipids (PG 20:0, Octadecenal, 9,10-Dihydroxy-octadecenoic acid, Palmitoleic acid, PA 18:4) and one amino acid derivate (Acetylglutamic acid) which presented significant score during Partial Least-Squares Discriminant Analysis. While it is early to attest the possible impact of such molecules in the CRC microenvironment, these results open new avenues for further studies focused in the energy metabolism at the cross-talk of colorectal canceradipocytes.