Multiomics Study of Cancer Growth

Cancer tumor cells are capable of adapting themselves to exploit their microenvironment in the body in order to grow. Cancer cells often metastasize in the liver, indicating that tumors are able to use hepatocytes, which are the main type of liver cell. Researchers do not fully understand interactions between tumors and hepatocytes, but these interactions are vital to the tumors’ ability to survive and grow.

In a study incorporating multiomics methods, including liquid chromatography and high-resolution, high-mass-accuracy mass spectrometry-based untargeted metabolomics, ¹³C-stable isotope tracing, and RNA sequencing, several MSI PIs and staff members studied the liver microenvironment to understand how co-localized primary hepatocytes and a colon adenocarcinoma cell line, SW480, interacted. They found a number of changes in the environment that allow tumors to survive and grow. More research is indicated, but this study supports the use of a bioinformatics approach to study metabolic crosstalk and discovery of potential therapeutic targets in preclinical models of the tumor microenvironment. 

This study was published in the International Journal of Molecular Sciences: Deciphering colorectal cancer–hepatocyte interactions: A multiomics platform for interrogation of metabolic crosstalk in the liver–tumor microenvironments.

MSI PIs at the University of Minnesota who participated in the study include:

• Assistant Professor Justin Hwang (Department of Medicine, Masonic Cancer Center)
• Assistant Professor Sandra E. Safo (Division of Biostatistics and Health Data Science)
• Professor David K. Wood (Department of Biomedical Engineering)
• Professor Kaylee Schwertfeger (Department of Laboratory Medicine and Pathology, Masonic Cancer Center)

Dr. Yinjie Qiu and Dr. Braedan McCluskey, who are members of MSI’s Bioinformatics group, also participated in this study.

Image description: Multiomics study of co-cultures of primary hepatocytes and SW480s. (A) Scheme of 2D co-culture system and timeline for cell collection. After growth arrest, 3T3J2s were plated with freshly thawed primary rat hepatocytes for 7 days, and then a subset of these plates received SW480s. After 3 days of co-culturing, all media and cells were collected for analysis. (B) Omics coverage of co-cultured groups included broad metabolomic coverage utilizing NMR- and LC-MS/MS-based approaches and bulk RNA sequencing. These data were integrated using univariate approaches to interrogate the impact of metabolic changes on tumor transcriptional profiles. Abbreviations: HJ, hepatocyte+3T3-J2 co-culture; SJH, SW480+3T3-J2+hepatocyte co-culture; SJ, SW480+3T3-J2 co-culture; NMR, nuclear magnetic resonance; LC-MS/MS, liquid chromatography hyphenated with tandem mass spectrometry. Image and description, AB Nelson, et al., International Journal of Molecular Sciences 26(5) (2025). doi: 10.3390/ijms26051976.