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

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.

Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3(2H)-Dione Moiety as Potential Antioxidant, Antimicrobial, and Anticancer Agents

“…Caco-2 cells seem to be more sensitive to our compounds compared with HCT-116 cells, and this result is in agreement with chemosensitivity properties of the two lines [35].…”

“…Both cell lines are models of colorectal adenocarcinoma; however, each cell line represents diferent histological grade of colon cancer. Caco-2 is a model of less metastatic, less invasive, and more diferentiated colon cancer cells; however, HCT-116 is known to be a poorly diferentiated and highly invasive cell line, and it is one of the higher chemoresistant colon cell lines [35].…”

The Mechanical and Biological Performance of Photopolymerized Gelatin‐Based Hydrogels as a Function of the Reaction Media

“…In addition, and just as explained for Caco‐2 cells, the mechanical behavior of the hydrogels is a relevant parameter. Stiffer substrates are known to lead to a higher cell proliferation [ 42 ] and in our case where Young's Moduli sharply rises from 2.1 kPa in DG0‐DG0 hydrogels to 11.6 kPa for PBS‐DG0, it is not surprising that HCT‐116 cells better proliferated on the latter ones. This specific biological response as a function of the hydrogel stiffness highlights how mechanics and biological properties are highly correlated.…”

Tumor Microenvironment in Colorectal Cancer Development: A Review of 3D Study Analysis

“…Colonic adenocarcinoma cells attenuated to hypoxia produce smaller tumors than control cells [25]. Chiang CT demonstrated that the growth of highly aggressive colorectal cancer is affected by oxygen levels, as well as response to chemotherapy in which hypoxia has a protective effect against oxaliplatin-induced cytotoxicity in the plastics and liver extracellular matrix used [28].…”