New advances on critical implications of tumor- and metastasis-initiating cells in cancer progression, treatment resistance and disease recurrence
M. Mimeault1,3 and S.K. Batra1,2,3
1Department of Biochemistry and Molecular Biology, 2Department of Pathology and Microbiology and 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Offprint requests to: Drs. Murielle Mimeault and Surinder K. Batra, Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA. e-mail: mmimeault@unmc.edu or sbatra@unmc.edu
Summary. Accumulating lines of experimental evidence have revealed that the malignant transformation of multipotent tissue-resident adult stem/progenitor cells into cancer stem/progenitor cells endowed with a high self-renewal capacity and aberrant multilineage differentiation potential may be at origin of the most types of human aggressive and recurrent cancers. Based on new cancer stem/progenitor cell concepts of carcinogenesis, it is suggested that a small subpopulation of highly tumorigenic and migrating cancer stem/progenitor cells, also designated as cancer- and metastasis-initiating cells, can provide critical roles for primary tumor growth, metastases at distant tissues and organs, treatment resistance and disease relapse. Particularly, cancer initiation and progression to locally invasive and metastatic stages is often associated with a persistent activation of distinct developmental signaling pathways in these immature cells during epithelial-mesenchymal transition program. The signaling cascades that are often deregulated in cancer stem/progenitor cells include hedgehog, epidermal growth factor receptor (EGFR), Wnt/ß-catenin, NOTCH, polycomb gene product BMI-1 and/or stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4). Importantly, the results from recent investigations have also indicated that different cancer subtypes may harbor distinct subsets and/or number of cancer-initiating cells during cancer progression as well as before or after therapy initiation and disease recurrence. Therefore, the identification of the molecular transforming events that frequently occur in cancer- and metastasis-initiating cells versus their differentiated progenies is of immense interest to develop new targeting approach for improving current therapies against aggressive, metastatic, recurrent and lethal cancers. Histol Histopathol 25, 1057-1073 (2010)
Key words: Cancer stem/progenitor cells, Solid tumors, Epithelial-mesenchymal transition, Invasion, Metastases, Treatment resistance, Molecular therapeutic targets, Cancer therapies
DOI: 10.14670/HH-25.1057