New advances on critical implications of tumorand metastasis-initiating cells in cancer progression, treatment resistance and disease recurrence

M. Mimeault, S. K. Batra

Research output: Contribution to journalReview articlepeer-review

46 Scopus citations


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 epithelialmesenchymal 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.

Original languageEnglish (US)
Pages (from-to)1057-1073
Number of pages17
JournalHistology and Histopathology
Issue number8
StatePublished - Aug 2010


  • Cancer stem/progenitor cells
  • Cancer therapies
  • Epithelial-mesenchymal transition
  • Invasion
  • Metastases
  • Molecular therapeutic targets
  • Solid tumors
  • Treatment resistance

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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