Research has brought about a host of discoveries in immunotherapy and in the use of CAR-T cells, which have translated into better cancer treatment and higher remission rates. However, this doesn’t mean that there is now a magic cure for cancer. This may be because the right cells for targeted cancer treatment have not yet been identified.
Cancer Stem Cells and CSC Hypothesis
Now it is known that there is a subclass of cancer cells called cancer stem cells (CSCs). Cancer stem cells (CSCs) are malignant in their properties but share the stem cell characteristics of self-renewal and pluripotency. Thus they can differentiate into any of the numerous types of cells that are found in tumors.
It was almost 150 years ago that Julius Cohnheim came up with the CSC hypothesis. This is also called the embryonal rest theory, and suggests that cancer develops non-spontaneously from cancerous remnants of embryonic-like cells within differentiated tissue.(1) This remained an unsupported hypothesis until 1994. At this point leukemia-initiating stem cells, or LSCs, found in the blood of leukemia patients, were found to be able to bring about acute myelogenous leukemia (AML) in mice with severe combined immunodeficiency (SCID) when injected into them.(2)
This was shown in experiments conducted by Dick et al. Other studies went on to show that a large variety of stem cell markers like CD133, CD44, and CD24 could be found on the cell surface of CSCs within solid tumors in humans, such as tumors of the colon, pancreas, ovary, brain, breast, liver, prostate, skin and melanomas. (3-6) Figure 1 shows this relationship. (Figure 1 based on 7)
CSCs are also interesting because they show resistance to a number of cancer treatments. More research is urgently needed to find out more about the way these cells act in cancer prognosis, tumor progression, and treatment strategies, so that CSC elimination may turn out to be the key factor in long-term survival of cancer patients.
The use of markers on cells to isolate specific subpopulations of tumor cells, namely, CSCs, has helped to gain greater insight into how plastic and heterogeneous these cells really are. Such markers include a wide variety of surface molecules, such as CD44 (15675-1-AP), CD24 (18330-1-AP), CD133 (18470-1-AP) or LC3B (18725-1-AP), seen in Figures 2 and 3 respectively.
Besides their stem cell properties, CSCs have become a focus of pharmacological studies due to their resistance to many cancer therapies. Although further investigation regarding CSCs is still needed, there is evidence that these cells play an important role in the prognosis of cancer, progression, and therapeutic strategy. In other words, long-term patient survival may depend on the elimination of CSCs.
The ability to isolate pure CSC populations using cellular markers has led to advances in our understanding of the heterogeneity and plasticity of the CSC phenotype. These markers include a broad spectrum of surface molecules such as CD44 (15675-1-AP), CD24 (18330-1-AP), CD133 (18470-1-AP, Figure 2), or LC3B (18725-1-AP, Figure 3).
Revolutionary Target for Cancer Treatment
Studies are showing more evidence that the CSC hypothesis is verifiable and that CSCs are a potentially revolutionary target for cancer treatment. Stem cells resist many cell insults that would damage many other cells, and this has led to the suggestion that the therapeutic sensitivity of CSCs could be increased by inhibiting either the stem cell characteristics or other linked pathways such as Notch, hedgehog, Wnt or others.
Stem cell characteristics are maintained chiefly by the stem cell’s special place in biological development. In the same way the CSC group of cells is enhanced by a number of connections between the micro-environmental factors and the connections between them and the tumor.
Thus breaking these relationships could be the vital factor in making them more susceptible to treatment. In addition, understanding CSCs better could help gain a picture of how and what new stem cell routes come into play as a tumor progresses, and this in turn would be very useful in helping to shape future treatments and design clinical trials.
- Cells of origin in cancer.
- A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.
- Identification and targeting of cancer stem cells.
- Identification of human brain tumour initiating cells.
- The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer
- ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome.
- In vitro models of cancer stem cells and clinical applications.
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