Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity

PLoS One. 2012;7(10):e45647. doi: 10.1371/journal.pone.0045647. Epub 2012 Oct 24.

Abstract

Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • Flow Cytometry
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Neoplastic Stem Cells / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents

Grants and funding

Genentech, Inc. funded this research. The study was funded by Genentech, Inc. through the employment (at the time of the study) of Ganapati V. Hegde, Cecile de la Cruz, Jeffrey Eastham-Anderson and Erica L. Jackson. These authors contributed to all aspects of the study.