High-throughput microscopy reveals the impact of multifactorial environmental perturbations on colorectal cancer cell growth

• Published in: Gigascience 2021-04, Vol.10 (4)
• Main Authors: Chiang, Chun-Te, Lau, Roy, Ghaffarizadeh, Ahmadreza, Brovold, Matthew, Vyas, Dipen, Juárez, Edwin F, Atala, Anthony, Agus, David B, Soker, Shay, Macklin, Paul, Ruderman, Daniel, Mumenthaler, Shannon M
• Format: Article
• Language: English
• Subjects: Biocompatibility; Bioengineering; Biomechanics; Cancer; Cell culture; Cell growth; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms; Cytotoxicity; Datasets; Dynamic models; Extracellular Matrix; Hepatocytes; Humans; Hypoxia; In vivo methods and tests; Liver; Liver cancer; Liver diseases; Mechanical properties; Metastases; Metastasis; Metastatic seeding; Microscopy; Oxaliplatin; Oxygen; Perturbation; Phenotypes; Phenotypic plasticity; Stroma; Tumor cell lines; Tumor cells; Tumor Microenvironment; Tumors
• ISSN: 2047-217X; 2047-217X
• DOI: 10.1093/gigascience/giab026

Abstract Background Colorectal cancer (CRC) mortality is principally due to metastatic disease, with the most frequent organ of metastasis being the liver. Biochemical and mechanical factors residing in the tumor microenvironment are considered to play a pivotal role in metastatic growth and response to therapy. However, it is difficult to study the tumor microenvironment systematically owing to a lack of fully controlled model systems that can be investigated in rigorous detail. Results We present a quantitative imaging dataset of CRC cell growth dynamics influenced by in vivo–mimicking conditions. They consist of tumor cells grown in various biochemical and biomechanical microenvironmental contexts. These contexts include varying oxygen and drug concentrations, and growth on conventional stiff plastic, softer matrices, and bioengineered acellular liver extracellular matrix. Growth rate analyses under these conditions were performed via the cell phenotype digitizer (CellPD). Conclusions Our data indicate that the growth of highly aggressive HCT116 cells is affected by oxygen, substrate stiffness, and liver extracellular matrix. In addition, hypoxia has a protective effect against oxaliplatin-induced cytotoxicity on plastic and liver extracellular matrix. This expansive dataset of CRC cell growth measurements under in situ relevant environmental perturbations provides insights into critical tumor microenvironment features contributing to metastatic seeding and tumor growth. Such insights are essential to dynamical modeling and understanding the multicellular tumor-stroma dynamics that contribute to metastatic colonization. It also establishes a benchmark dataset for training and testing data-driven dynamical models of cancer cell lines and therapeutic response in a variety of microenvironmental conditions.