Project Details
Projekt
Genetic and functional heterogeneity within the tumor-initiating cell compartment of human colon cancer
Applicant
Dr. Claudia Ball
Subject Area
General and Visceral Surgery
Term
from 2009 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 101804013
Novel drugs that are directly cytotoxic or interfere with key regulators of colorectal cancer biology lead to remissions in most patients. However, the vast majority of patients with disseminated disease eventually die due to cancer cell resistance. Recently, rare tumor initiating ( stem ) cells have been described in different cancers which rebuild the tumor in immunodeficient mice, whereas the bulk of tumor cells is not capable of initiating tumors or metastases. The inherent drug resistance of such initiating cells is considered the reason for tumor relapse after an initial clinical response. However, few hard data is available to characterize the role of tumor-initiating cells in colon cancer biology or therapy resistance. The aim of this project is to gain a better understanding of cell cycle activity, drug sensitivity and clonal structure of the human colon cancer initiating cell compartment. Purification of cells in specific stages of the cell cycle combined with xenotransplantation in immunodeficient mice will allow defining the proliferative activity of colon cancer-initiating cells. High resolution tracking of cell divisions in vitro will be used to investigate whether a quiescent population of cancer-initiating cells exists in colon cancer and whether it is associated with resistance to chemotherapy. Lentiviral marking in combination with highly sensitive tracking of individual integration sites in primary tumors and subsequent metastases will lead to new insights into the clonal structure and relationship between primary tumor cells and their metastasis-initiating descendents. Characterization of the cell cycle biology of colon cancer-initiating cells and their contribution to metastasis formation will be used to design, model and test treatment protocols with specific activity against tumor-initiating cells.
DFG Programme
Clinical Research Units
Participating Persons
Professor Dr. Hanno Glimm; Manfred Schmidt, Ph.D.
