A consensus panel convened by the American Association of Cancer Research has defined a CSC as "a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor."12 It should be noted that this definition does not indicate the source of these cells—these tumor-forming cells could hypothetically originate from stem, progenitor, or differentiated cells.13 As such, the terms "tumor-initiating cell" or "cancer-initiating cell" are sometimes used instead of "cancer stem cell" to avoid confusion.
The CSC hypothesis therefore does not imply that cancer is always caused by stem cells or that the potential application of stem cells to treat conditions such as heart disease or diabetes, as discussed in other chapters of this report, will result in tumor formation. Rather, tumor-initiating cells possess stem-like characteristics to a degree sufficient to warrant the comparison with stem cells; the observed experimental and clinical behaviors of metastatic cancer cells are highly reminiscent of the classical properties of stem cells.
أكد عدة باحثون فرضية الخلايا الجذعية بإثبات أن خلية ورمية واحدة يمكنها أن تولد سلالة متغايرة وتعطي ورماً جديداً.
umour cells may be passaged directly on plastic or embedded in Matrigel, a substitute for the basement membrane. Each colony-forming assay represents a read-out for progenitor cell activity. Stem cells and progenitors cannot be distinguished in these assays.
سنرجع لهذه الصورة
Colorectal - centric view of tumor progression. (a) Normal tissue - resident
stem cell populations, such as the colon stem cell (red), which is localized at the base
of the crypt, have both the unique ability to self - renew (relative ability indicated by a
black triangle) and to generate the differentiated progeny that comprise this tissue.
Progeny of the colon stem cell include highly proliferative transit amplifying cells
(progenitor; gray) and terminally differentiated enteroendocrine or goblet cells (white).
(b) In tumors where the CSC lies at the level of the tissue - resident stem cell, increased
symmetric division fates result in expanded stem cell numbers and thus, a similar
expansion of their resulting progeny. This sudden increase in cells vying for space within
a tissue may manifest as an adenocarcinoma. (c) Aggressive, end - stage carcinomas
might result from the gain of self - renewal capacity by an already proliferative progenitor cell pool with limited to no differentiation capacity, often resulting in amorphous, largely undifferentiated tumors.
Wnt, Shh, and Notch pathways have been shown to contribute to the self-renewal of stem cells and/or progenitors in a variety of organs, including the haematopoietic and nervous systems. When dysregulated, these pathways can contribute to oncogenesis. Mutations of these pathways have been associated with a number of human tumours, including colon carcinoma and epidermal tumours (Wnt), medulloblastoma and basal cell carcinoma (Shh), and T-cell leukaemias (Notch).