Abstract B13: High-content imaging to quantitate colorectal cancer associated fibroblast heterogeneity

Autor: Shannon M. Mumenthaler, Oscar Chen, Colleen M. Garvey, Roy Lau
Rok vydání: 2017
Předmět:
Zdroj: Cancer Research. 77:B13-B13
ISSN: 1538-7445
0008-5472
Popis: Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment known to influence various aspects of tumor progression, including response to therapy. However, this stromal cell subtype is extremely heterogeneous, both between and within individual tumors. Targeting of the CAF population has not been successful in the clinical setting, which could be due in part to the myriad of functions of different CAF subpopulations. In order to elucidate the overall implications of CAF heterogeneity, we gathered quantitative phenotypic data using a novel high-content imaging platform. Specifically, we calculated several morphological parameter values and estimated birth and death rates of individual populations of CAFs isolated from colorectal cancer patients. We also performed co-culture experiments with tumor cells and characterized the influence of different CAF populations on tumor evolutionary dynamics (i.e. birth and death rates) in response to drug treatment. Further, these features were correlated to molecular analyses (i.e. -smooth muscle actin and fibroblasts activated protein expression) and patient outcome (i.e. sites of metastasis). We observed high levels of heterogeneity in cell area and cell roundness as well as altered rates of growth in response to perturbations in oxygen levels. This quantitative method for investigating multiple cellular phenotypes provides novel insight into patient-level heterogeneity and its possible implications on response to drug. Citation Format: Colleen M. Garvey, Oscar Chen, Roy Lau, Shannon M. Mumenthaler. High-content imaging to quantitate colorectal cancer associated fibroblast heterogeneity. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B13.
Databáze: OpenAIRE