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Metastasis of osteosarcoma is an important adverse factor affecting patients’ survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100$\mu$M, 24h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment’s inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin’s dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Solasonine (SS) is a natural glycoalkaloid compound that has been reported to possess a significant anticancer function. However, its anticancer effects and related mechanisms in osteosarcoma (OS) have not been studied. This study sought to investigate the impact of SS on the growth of OS cells. OS cells were treated with different concentrations of SS for 24h, and the results showed that SS attenuated the survival of OS cells in a dose-dependent manner. Additionally, SS suppressed cancer stem-like properties and epithelial–mesenchymal transition (EMT) by inhibiting aerobic glycolysis in OS cells in an ALDOA-dependent manner. Additionally, SS reduced the levels of Wnt3a, $\beta$-catenin, and Snail in OS cells in vitro. Furthermore, Wnt3a activation reversed the SS-induced inhibition of glycolysis in OS cells. Collectively, this study discovered a novel effect of SS in inhibiting aerobic glycolysis, in addition to cancer stem-like features and EMT, implying that SS could be a therapeutic candidate for OS treatment.

The detection, in a wide variety of cancer types, of a population of highly tumorigenic cells that exhibit self-renewal and multipotency, which are hallmarks of stem cells, has transformed the current view of tumor initiation, progression, and treatment. Here, we develop and analyze a mathematical model for tumor growth that is based on the current biological understanding of the processes that underlie cellular expansion under the hierarchical guidelines of the cancer stem cell (CSC) hypothesis. Important features of the model include (i) a nonlinear probability of CSC self-renewal that reflects the fact that this key type of stem cell division can be regulated by extrinsic and intrinsic chemical signaling as well as environmental (niche) constraints and (ii) an amplification factor that captures the transient amplifying divisions that are a defining characteristic of progenitor cells. We present a thorough mathematical analysis of the model and highlight the conditions required for tumors to evolve toward either bounded or exponential growth. Numerical simulations further illustrate the impact of the various parameters on the tumor growth rate and on the heterogeneous cellular composition, which varies during progression.

Of all cancers, pancreatic cancer has a significantly low rate of survival, mostly due to lack of early screening. Thus, once detected, pancreatic cancer is usually in later stages, reducing the likelihood of full recovery. The most common treatment strategy is chemotherapy, although several immunotherapeutic drugs show promising results in extending the patient’s lifespan. In this paper, we provide a validated mathematical model for the pancreatic cancer after fitting the parameter values, such as tumor growth rate, inverse carrying capacity, activation and decay rate of pancreatic stellate cells, with the use of the experimental data presented by Cioffi et al. cioffi2015inhibition For treatments with the chemotherapeutic drugs, Abraxane and Gemcitabine, and the immunotherapeutic drug, Anti-CD47, we modified the model accurately and compared the simulation results with the experimental data not only to model pancreatic cancer treatment correctly but also to move forward with other drug trials. Then, we include the cancer stem cells, which are known to initiate tumors and cause a relapse post-chemotherapy, per cancer stem cell hypothesis so that cancer progression can be assessed based on this phenomenon. In addition, we investigate optimal drug protocols. We find out that the most effective treatment is dual therapy due to extending survival time when compared to other drugs. Moreover, this study reveals that drug dose is more effectual than frequency of drug injection on account of different treatment scheduling with the same dose over a week. The model could be a starting point to investigate pancreatic cancer progression based on cancer stem cell hypothesis and shed light on novel drug discoveries.

This article deals about the new trends in biotechnology and pharmaceutical development in Taiwan.

A model with spherical symmetry is proposed. We analyze the appropriate parameters of cell differentiation for different kinds of cells (Cancer Stem Cells (CSC) and Differentiated Cells (DC)). The plasticity (capacity to return from a DC to its previous state of CSC) is taken into account. Following this hypothesis, the dissemination of CSCs to another organ is analyzed. The location of the cells in the tumor and the plasticity range for possible metastasis is discussed.

Stem cells possess a distinctive capability for self-renewal and differentiation which enables their characterization. An increased understanding of stem cell biology toward the end of the 20th century, and the realization of their uncanny similarities with cancer cell behavior, led to the proposal of the provocative “stem cell theory of cancer” in the early part of this century. The two tenets of this theory are that (i) cancers originate in normal, adult stem cells and (ii) cancers harbor a subpopulation of “cancer stem cells” (CSCs) that drive cancer growth. Identification of CSCs from several cancers and their intricate association with drug resistance has revolutionized the field of cancer biology by changing our understanding of cancer development and strategies to treat cancer. Our book chapter aims to broaden the current knowledge on CSCs by providing a summary of their origin, isolation, and targeting strategies with special emphasis on breast CSCs.

CD44 is a well-characterized adhesion molecule with multi-faceted biological functions. Earlier studies have implicated CD44 in the invasion and metastasis of multiple human cancers. Newly generated data suggest that tumor cells expressing CD44 may be intrinsically different from the bulk CD44⁻ cells and that its expression may mark a population of tumor-initiating cells called cancer stem cells (CSCs). In this review, we succinctly summarize the evidence of CD44 as a CSC marker and also discuss the possibility of targeting CD44-expressing CSCs.