Posted by: Dan | January 9, 2007

Metastasis Review

I’m way behind in blogging about papers in cell and molecular biology, having been taking it easy over the quiet time here on campus. But I’m slowly getting around to the pile of papers on my desk, and one interesting review on cancer metastasis can be found way back in the November 17th issue of Cell. The summary of Gupta and Massagué’s paper:

Metastasis occurs when genetically unstable cancer cells adapt to a tissue microenvironment that is distant from the primary tumor. This process involves both the selection of traits that are advantageous to cancer cells and the concomitant recruitment of traits in the tumor stroma that accommodate invasion by metastatic cells. Recent conceptual and technological advances promote our understanding of the origins and nature of cancer metastasis

It’s a great review. However, with my previous post in mind, I feel the need to comment on their bit about cancer stem cells, referencing Pardal et al. (2003). Gupta and Massagué qualify their reference to cancer stem cells appropriately, however:

These tumor-initiating cells are sometimes referred to as cancer stem cells (Pardal et al., 2003). As was originally demonstrated for hematological malignancies (Bonnet and Dick, 1997), solid malignancies of the breast and brain have recently been shown to contain cells with such tumor-initiating capacity (Al-Hajj et al., 2003 and Singh et al., 2004). When isolated, these cells were capable of giving rise to all other transformed cellular phenotypes (as defined by cell surface markers) observed in the original tumor. Additionally, they were capable of initiating secondary tumors from very low numbers of transplanted cells (a surrogate for self-renewal activity). However, the idea that self renewal in solid tumors is a property of only a tiny cell subpopulation in a tumor mass is currently supported by limited evidence. Moreover, if self-renewing tumor cells are the only cells capable of generating secondary growths, then one might expect that the prevalence of tumor-initiating cells in a tumor would reflect the overall proclivity for metastatic recurrence. This, however, has yet to be shown. Regardless of the relative abundance of self-renewing cells in primary tumors, a capacity for tumor initiation is a must for the reestablishment of the tumor by a few surviving cells in a distant metastatic location.

This is an excellent description of “tumor initiation,” and one that takes into account the fact that stem cell lineages may not be the only explanation for self-renewal and clonal expansion in cancer cells. Indeed, this description fits better with the evolving ecosystem model of cancer than the stem cell model. That said, yes, pathways mediating self-renewal and proliferative capacity in stem cells is an excellent place to look for studying the capacity for tumor initiation. But I’m repeating my previous post now…

The rest of the review is just as good, and nicely overviews the full range of knowledge on cancer metastasis.

References::

  • Gupta G, Massagué J. Cancer Metastasis: Building a Framework. Cell. 2006 Nov 17;127(4):679-95. Pubmed
  • Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003 Dec;3(12):895-902. pubmed
  • Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
    Nat Med. 1997 Jul;3(7):730-7. Pubmed
  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8. Pubmed
  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004 Nov 18;432(7015):396-401. Pubmed

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