The bed and the bugs: Interactions between the tumor microenvironment and cancer stem cells

Zafira Castaño, Christine M. Fillmore, Carla F. Kim, Sandra S. McAllister

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Tumors have been increasingly recognized as organs with a complexity that approaches, and may even exceed, that of healthy tissues. When viewed from this perspective, the biology of a tumor can be understood only by studying tumor cell heterogeneity and the microenvironment that is constructed during the course of tumorigenesis and malignant progression. Recent work has revealed the existence of cancer stem cells, the "bugs", with the capacity for self-renewal and tumor propagation. In addition, it is now recognized that the tumor microenvironment, the "bed", plays a critical role in supporting cancer stem cells and also may promote neoplasia and malignant progression. The interdependence of the cell-intrinsic features of cancer, including the cancer stem cell "bugs" and the tumor microenvironment "bed", is only beginning to be understood. In this review, we highlight the rapidly evolving concepts about the interactions between tumor stem cells and their microenvironment, the insights gained from studying their normal tissue counterparts, and the questions and controversies surrounding this area of research, with an emphasis on breast and lung cancer. Finally, we address evidence supporting the notion that eliminating the bed as well as the bugs should lead to more effective and personalized cancer treatments that improve patient outcome.

Original languageEnglish
Pages (from-to)462-470
Number of pages9
JournalSeminars in Cancer Biology
Issue number5-6
StatePublished - Oct 2012

Bibliographical note

Funding Information:
We acknowledge the great strides made by a large number of investigators in these areas of research and regret that we could not include all of them and their work in this review. This work was supported by funds from the Ladies Auxiliary to the Veterans of Foreign Wars (CMF) ; RO1 HL090136 , U01 HL100402 , American Cancer Society Research Scholar Grant # RSG-08-082-01-MGO , the V Foundation for Cancer Research , a Basil O’Conner March of Dimes Starter Award, and the Harvard Stem Cell Institute (CFK) ; the Harvard Stem Cell Institute, Breast Cancer SPORE Developmental Project Award, and DFHCC Nodal Award (SSM). We thank Jamie Brien, Hematology Division, Brigham and Womeńs Hospital, for help in preparation of the manuscript.


  • Breast cancer
  • Cancer stem cells
  • Lung cancer
  • Stem cells
  • Tumor heterogeneity
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research


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