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

GigaScience ◽  
2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Chun-Te Chiang ◽  
Roy Lau ◽  
Ahmadreza Ghaffarizadeh ◽  
Matthew Brovold ◽  
Dipen Vyas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Matrix ◽  
Cell Growth ◽  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Response To Therapy ◽  
Model Systems ◽  
Cell Phenotype ◽  
Environmental Perturbations ◽  
Drug Concentrations

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.

scholarly journals KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

2019 ◽  
Vol 189 (10) ◽  
pp. 1916-1932 ◽  
Author(s):  
Francesco Caiazza ◽  
Katarzyna Oficjalska ◽  
Miriam Tosetto ◽  
James J. Phelan ◽  
Sinéad Noonan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Regulatory Protein ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Growth

scholarly journals Functional melanoma cell heterogeneity is regulated by MITF-dependent cell-matrix interactions

2020 ◽  
Author(s):  
Loredana Spoerri ◽  
Crystal A. Tonnessen-Murray ◽  
Gency Gunasingh ◽  
David S. Hill ◽  
Kimberley A. Beaumont ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cancer Cell ◽  
Melanoma Cell ◽  
Focal Adhesions ◽  
Response To Therapy ◽  
Fine Tuning ◽  
Cell Phenotype ◽  
Cell Heterogeneity ◽  
Cell Contractility

SummaryPhenotypic and functional cancer cell heterogeneity limits the efficacy of targeted and immuno-therapies. The transcription factor MITF is known to regulate melanoma cell plasticity and, consequently, response to drugs. However, the underlying mechanisms of this phenomenon remain incompletely understood. Here, we show that MITF levels control functional melanoma cell heterogeneity by fine-tuning the ability to contract the extracellular matrix, the maturation of focal adhesions and ROCK-mediated melanoma cell contractility. Modulation of MITF expression alters extracellular matrix organization, melanoma cell morphology and solid stress in three-dimensional melanoma spheroids, thereby accounting for spatial differences in cell cycle dynamics. Together, our data identify MITF as a master regulator of the melanoma micro-architecture and point towards novel targeting strategies for cancer cell heterogeneity.SignificanceDevelopment of drug resistance is a major cause of melanoma therapy failure. The role of MITF in melanoma response to therapy has been discussed controversially, which can be explained, at least in part, through the rheostat model linking MITF activity to cell proliferation. Heterogeneity is widely associated with therapy resistance, however, whether cell phenotype switching, mediated by MITF, is responsible for treatment resistance is not known. Our findings provide an in-depth mechanistic understanding of the MITF-mediated regulation of cell cycle behavior and physical regulation of the tumor architecture. As MITF is not amenable to direct drug targeting, the identification of mediators of MITF-triggered functional heterogeneity reveals novel targets that can be deployed to control this phenomenon.

scholarly journals Extracellular Matrix-dependent Pathways in Colorectal Cancer Cell Lines Reveal Potential Targets for Anticancer Therapies

2016 ◽  
Vol 36 (9) ◽  
pp. 4559-4568 ◽  
Author(s):  
VAIDOTAS STANKEVICIUS ◽  
GINTAUTAS VASAUSKAS ◽  
RIMANTE NOREIKIENE ◽  
KAROLINA KUODYTE ◽  
MINDAUGAS VALIUS ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Matrix ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines

scholarly journals Enzalutamide response in a panel of prostate cancer cell lines reveals a role for glucocorticoid receptor in enzalutamide resistant disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rebecca Smith ◽  
Moqing Liu ◽  
Tiera Liby ◽  
Nora Bayani ◽  
Elmar Bucher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glucocorticoid Receptor ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Response To Therapy ◽  
Model Systems ◽  
Prostate Cancer Cell Lines

AbstractRepresentative in vitro model systems that accurately model response to therapy and allow the identification of new targets are important for improving our treatment of prostate cancer. Here we describe molecular characterization and drug testing in a panel of 20 prostate cancer cell lines. The cell lines cluster into distinct subsets based on RNA expression, which is largely driven by functional Androgen Receptor (AR) expression. KLK3, the AR-responsive gene that encodes prostate specific antigen, shows the greatest variability in expression across the cell line panel. Other common prostate cancer associated genes such as TMPRSS2 and ERG show similar expression patterns. Copy number analysis demonstrates that many of the most commonly gained (including regions containing TERC and MYC) and lost regions (including regions containing TP53 and PTEN) that were identified in patient samples by the TCGA are mirrored in the prostate cancer cell lines. Assessment of response to the anti-androgen enzalutamide shows a distinct separation of responders and non-responders, predominantly related to status of wild-type AR. Surprisingly, several AR-null lines responded to enzalutamide. These AR-null, enzalutamide-responsive cells were characterized by high levels of expression of glucocorticoid receptor (GR) encoded by NR3C1. Treatment of these cells with the anti-GR agent mifepristone showed that they were more sensitive to this drug than enzalutamide, as were several of the enzalutamide non-responsive lines. This is consistent with several recent reports that suggest that GR expression is an alternative signaling mechanism that can bypass AR blockade. This study reinforces the utility of large cell line panels for the study of cancer and identifies several cell lines that represent ideal models to study AR-null cells that have upregulated GR to sustain growth.

Sign in / Sign up

Export Citation Format

Share Document