English Version
The deepening of our understanding of normal biology has made it clear that stem cells have a critical role not only in the generation of complex multicellular organisms, but also in the development of tumors. Recent findings support the concept that cells with the properties of stem cells are integral to the development and perpetuation of several forms of human cancer. Eradication of the stem-cell compartment of a tumor also may be essential to achieve stable, long-lasting remission, and even a cure, of cancer. Advances in our knowledge of the properties of stem cells have made specific targeting and eradication of cancer stem cells a topic of considerable interest. In this article, we discuss the properties of cancer stem cells, outline initial therapeutic strategies against them, and present challenges for the future.
Background and Definitions
Stem cells occur in many different somatic tissues and are important participants in their physiology (Fig. 1). Populations of cells that derive from stem cells are organized in a hierarchical fashion, with the stem cell residing at the apex of the developmental pathway (Fig. 2). Stem cells have three distinctive properties: selfrenewal (i.e., at cell division, one or both daughter cells retain the same biologic properties as the parent cell), the capability to develop into multiple lineages, and the potential to proliferate extensively. The combination of these three properties makes stem cells unique. The attribute of self-renewal is especially notable, because its subversion is highly relevant to oncogenesis and malignancy. Aberrantly increased self-renewal, in combination with the intrinsic growth potential of stem cells, may account for much of what is considered a malignant phenotype.
Many studies performed over the past 30 to 40 years, when viewed collectively, have shown that the characteristics of stem-cell systems, the specific stem-cell properties described above, or both, are relevant to some forms of human cancer. Biologically distinct and relatively rare populations of “tumor-initiating” cells have been identified in cancers of the hematopoietic system, brain, and breast. Cells of this type have the capacity for self-renewal, the potential to develop into any cell in the overall tumor population, and the proliferative ability to drive continued expansion of the population of malignant cells. Accordingly, the properties of tumor-initiating cells closely parallel the three features that define normal stem cells. Malignant cells with these functional properties have been termed “cancer stem cells” (Fig. 2).
Given these features, it is possible that cancer stem cells arise by mutation from normal stem cells. However, several lines of evidence indicate that cancer stem cells can also arise from mutated progenitor cells. Such progenitors (also known as “transit-amplifying cells”) can possess substantial replicative ability, but they do not usually have the self-renewal capacity of stem cells. To become a cancer stemcell, a progenitor cell must acquire mutations that cause it to regain the property of self-renewal. A detailed discussion of the origins of cancer stem cells is beyond the scope of this review, but it is important to acknowledge the possibility that multiple pathways and processes can give rise to cancer stem cells.
Journals for full download on the link below
Stem cells occur in many different somatic tissues and are important participants in their physiology (Fig. 1). Populations of cells that derive from stem cells are organized in a hierarchical fashion, with the stem cell residing at the apex of the developmental pathway (Fig. 2). Stem cells have three distinctive properties: selfrenewal (i.e., at cell division, one or both daughter cells retain the same biologic properties as the parent cell), the capability to develop into multiple lineages, and the potential to proliferate extensively. The combination of these three properties makes stem cells unique. The attribute of self-renewal is especially notable, because its subversion is highly relevant to oncogenesis and malignancy. Aberrantly increased self-renewal, in combination with the intrinsic growth potential of stem cells, may account for much of what is considered a malignant phenotype.
Many studies performed over the past 30 to 40 years, when viewed collectively, have shown that the characteristics of stem-cell systems, the specific stem-cell properties described above, or both, are relevant to some forms of human cancer. Biologically distinct and relatively rare populations of “tumor-initiating” cells have been identified in cancers of the hematopoietic system, brain, and breast. Cells of this type have the capacity for self-renewal, the potential to develop into any cell in the overall tumor population, and the proliferative ability to drive continued expansion of the population of malignant cells. Accordingly, the properties of tumor-initiating cells closely parallel the three features that define normal stem cells. Malignant cells with these functional properties have been termed “cancer stem cells” (Fig. 2).
Given these features, it is possible that cancer stem cells arise by mutation from normal stem cells. However, several lines of evidence indicate that cancer stem cells can also arise from mutated progenitor cells. Such progenitors (also known as “transit-amplifying cells”) can possess substantial replicative ability, but they do not usually have the self-renewal capacity of stem cells. To become a cancer stemcell, a progenitor cell must acquire mutations that cause it to regain the property of self-renewal. A detailed discussion of the origins of cancer stem cells is beyond the scope of this review, but it is important to acknowledge the possibility that multiple pathways and processes can give rise to cancer stem cells.
Journals for full download on the link below
RSS Feed 
Tidak ada komentar:
Posting Komentar