Resistance Mechanisms of Tumor Cells
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
It is worth mentioning that the concept of “cancer stem cells” in solid tumors was not known for a very long time; rather it became adapted from conceptional studies performed with hematological tumor models (as described by Bonnet and Dick, 1997), which were subsequently validated also for solid tumors (Jordan, 2004). The novel concept of cancer stem cells has changed the mind of many researchers and physicians, because all the treatment schedules that have been established in clinical studies over decades have been optimized for killing of the large tumor burden, rather than targeting specifically the very small compartment of cancer stem cells. Importantly, this stem cell population is not only responsible for the creation of the tumor bulk but also most likely the source for relapses in tumor patients.
Therapeutic Targeting of the Melanoma Stem Cell Population
Sanjiv S. Agarwala, Vernon K. Sondak in Melanoma, 2008
There is a growing body of evidence to suggest that cancers may arise from an oncogenically transformed population of stem cells. The cancer stem cell theory postulates that tumor formation, growth, and metastatic spread are driven by a minority population of tumor-initiating or cancer stem cells. Usefully, this hypothesis helps to explain a number of key observations that have vexed the cancer research community for many years. It has long been known that the majority of tumor cells are actually nontumorigenic and cannot be successfully transplanted into new hosts. This point is well illustrated by the fact that typical mouse xenograft experiments require the injection of one to two million cells to ensure tumor establishment. In a similar vein, the genetic model of cancer predicts that a serial acquisition of oncogenes and inactivation of tumor suppressors is required for oncogenic transformation. This model, which would require a 10- to 30-year time frame, has always been difficult to reconcile with relatively short life span of most somatic cells. The fact that stem cells are the longest-lived cells within the body fits well with the idea of a long-term acquisition of oncogenic mutations.
Introduction to Cell Biology
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
As with other cell behaviors discussed in this chapter, the process of differentiation can be used by cancer cells to promote tumorigenesis. Genes that are switched off in a terminally differentiated cell can be reexpressed because of oncogenic activity and this can alter the differentiation status of that cell. A key histological marker of aggressive disease is the degree of dedifferentiation within tumor tissue. Altered differentiation also underlies the ability of tumor cells to form metastases. During development, mesenchymal cells migrate to their respective positions within tissues where many then undergo terminal epithelial differentiation. Tumor cells can reverse this process by reexpressing mesenchymal genes and allowing epithelial cells to obtain a migratory phenotype. It is a hotly debated issue within the cancer field, however, as to whether de- or transdifferentiated cells actually represent the altered state of preexisting cells that were terminally differentiated, or whether these populations are derived from a stem cell or progenitor that had acquired oncogenic characteristics. Evidence suggests cancer stem cells may exist in certain tumor types and, if definitively proven, has far-reaching implications on the development of future cancer therapies.
Enhanced chemotherapeutic efficacy of the low-dose doxorubicin in breast cancer via nanoparticle delivery system crosslinked hyaluronic acid
Published in Drug Delivery, 2019
Qin Wang, Yinan Zhong, Wenting Liu, Zemin Wang, Liqin Gu, Xuejiao Li, Jiqing Zheng, Huan Du, Zhiyuan Zhong, Fang Xie
Cancer stem cells, which have a high proliferative potential, are responsible for tumor initiation, drug resistance, metastasis, and recurrence. Cancer stem cells of BC strongly express CD44, together with no or very low levels of CD24 (Supplemental Figure S2(A)). To identify whether surface CD44 and CD24 expression correlates with CSC phenotype, we collected CD44+CD24low/– and CD44+CD24+ populations, and tested each population in the cell sphere formation assay. CD44+CD24low/– MCF-7 cells grew as spheroids and cell colonies under our experimental conditions, whereas CD44+CD24+ MCF-7 cells did not (Supplemental Figure S2(B)). The transwell system assay showed that CD44+CD24low/– MCF-7 cells were significantly higher in metastasis than that of CD44+CD24+ MCF-7 cells (Supplemental Figure S2(C)).
The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell
Published in Nutrition and Cancer, 2020
Mustafa Hoca, Eda Becer, Hilal Kabadayı, Sevinç Yücecan, Hafize Seda Vatansever
Cancer stem cells have the capacity for self-renewal which enables them to differentiate into other types of malignant cells (10). The metastatic behavior of cancer stem cells is responsible for the progression of the disease. Therefore, targeting cancer stem cells is important for developing more effective treatment strategies (5). It is considered that inhibition of cancer stem cell activity might be a good approach in the treatment of cancer (7). A study conducted by Lee et al. (11) showed that CD133+ cells had higher tumorigenic and metastatic potential than CD44+ and CD24+ cells, suggesting that CD133 may be significant cell surface marker of pancreatic cancer stem cells. Cao et al. (12) demonstrated that quercetin can reduce the expression of CD133 in pancreatic cancer stem cells. Furthermore, resveratrol has potential inhibitory effects on migration, invasion and epithelial-mesenchymal transition (EMT) of both pancreatic cancer stem cells and pancreatic cancer cells (13,14). Previous studies have demonstrated that quercetin can decrease the migration ability of different cancer cell lines including oral cancer cells, breast cancer stem cells, and prostate cancer cells (15–17). On the other hand, many studies have shown that resveratrol can inhibit EMT ability of various cancer cell lines such as oral squamous cell carcinoma cells and prostate cancer cells (18,19).
Targeting genetic tool for long non-coding RNA of cancer stem cells with aptamer-guided nanocarriers
Published in Expert Opinion on Drug Delivery, 2021
Colloquially termed ‘immortal tumor-initiating cells,’ cancer stem cells represent tumor subpopulations that possess unlimited self-renewal and pluripotency attributes [1]. The classic cancer phenotypes, their aggressive nature, and chemotherapy resistance are largely attributable to cancer stem cells. Recent reviews by Shibata and Hoque (2019) and Zhou et al. (2017) highlighted that cancer stem cells’ rapid self-renewal and differentiation into diverse cancer lineages are the cradle to cancer initiation, progression, and heterogeneous expression [2,3]. The cancer stem cells, with altered metabolism and immune response evasion, give rise to chemo-resistant tumor populations [4]. They can enter into a state of quiescence that shields them from death which in turn facilitates tumor relapse [2,3]. A study by Nair and colleagues (2017) reported that cancer-associated fibroblasts, a key stromal component of tumor microenvironments that support cancer growth and survival, originate from cancer stem cells [5]. The cancer stem cells can rapidly recapitulate the migrating parent tumor through fibroblastic activities to succeed metastasis [6]. On this note, eradicating cancer stem cells is imperative in cancer treatment.
Related Knowledge Centers
- Animal Disease Model
- Metastasis
- Neoplasm
- Stem Cell
- Cancer
- Carcinogenesis
- Tumors of The Hematopoietic & Lymphoid Tissues
- Cell Type
- Relapse
- Fractional Kill