Are Breast Tumor Stem Cells Responsible for Metastasis and Angiogenesis?
Abstract
Despite advances in the early detection and treatment of breast cancer, the mortality rate for 20% of patients with recurrences and/or metastases is nearly 100%. Thus, it is critical to understand the mechanism of breast cancer metastasis to allow for better therapies targeted at the cellular culprits of metastasis. The current dogma of metastasis is that most primary tumor cells have low metastatic potential, but rare cells, less than one in 10 million, within large primary tumors acquire metastatic capacity through somatic mutation. The metastatic phenotype includes the ability to disseminate from the primary tumor, survive in blood or lymphatic circulation, invade distant tissues, and establish macroscopic metastatic nodules. This dogma is primarily supported by animal models in which highly metastatic clones can develop from poorly metastatic cell lines if the process is facilitated by the isolation of metastatic nodules, expansion of the cells in vitro, and injection of these selected cells into recipient mice. However, no direct evidence of this genetic selection model has been documented in human tumors. A recent report demonstrated that a subpopulation of breast tumor cells (CD44+/CD24-(low)/Lineage-) isolated from breast cancer patient samples, even as few as 200 cells, were able to give rise to bulky tumors, greater than 1 cm in diameter, in NOD/SCID mice. Moreover, this discrete cell population has the ability to proliferate extensively, and to give rise to diverse and more differentiated cell types with reduced developmental or proliferative potential, suggesting that these highly tumorigenic CD44+/CD24-(low)/Lineage-cells may, indeed, be breast tumor stem cells. With this information, the authors propose an alternate model of metastasis and hypothesize that the breast tumor stem cells are the subpopulation of cells that are present in the heterogeneous primary breast tumor and possess the unique properties of an angiogenic and metastatic phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA507596
Entities
People
- Quintin Pan
Organizations
- University of Michigan