Investigators studied metastatic deposits of prostate cancers with isoform-specific ΔNp63 and TAp63 antibodies. They identified p63-positive cells in only 3 of 42 metastatic prostate tumors, including 2/38 “usual-type” adenocarcinomas. ΔNp63 and TAp63 isoforms were present in the nuclei of < 1% of tumor cells in these metastases.
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Investigators found that active targeting nanoparticles displayed a superior DNA damage capability via enhanced-interactions with DNA and a significantly stronger effect in reducing cancer stem cell-like property of triple negative breast cancer cells, compared to conventional cisplatin and miriplatin.
[Journal of Controlled Release]
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Li, Y., Qian, D., Lin, H.-P., Xie, J., Yang, P., Maddy, D., Xiao, Y., Huang, X., Wang, Z., & Yang, C. (2020). Nanoparticle-delivered miriplatin ultrasmall dots suppress triple negative breast cancer lung metastasis by targeting circulating tumor cells. Journal of Controlled Release. https://doi.org/10.1016/j.jconrel.2020.10.015 Cite
Scientists established GC organoids (GCOs) and gradually treated them with higher concentrations of 5-FU. They successfully harvested four 5-FU-resistant GCOs, which were supported by significant changes in the expression of molecules related to 5-FU metabolism. Microarray analysis was peformed using three normal gastric organoids and three pairs of 5-FU-resistant and parental GCOs.
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Ukai, S., Honma, R., Sakamoto, N., Yamamoto, Y., Pham, Q. T., Harada, K., Takashima, T., Taniyama, D., Asai, R., Fukada, K., Naka, K., Tanabe, K., Ohdan, H., & Yasui, W. (2020). Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell. Oncogene, 1–14. https://doi.org/10.1038/s41388-020-01492-9 Cite
The authors advocate with substantial evidence the dynamic model of tumor propagation by exploring the specific cell types, reversible phenotypic plasticity between the tumorigenic leader seeds and the supporting follower cancer cells both in circulation and in solid tissue to accurately decipher tumor promoting clones and its role in metastatic dissemination and tumor re-growth.
Scientists demonstrated that, with direct cell-cell contact, tumor microenvironment-derived endothelial cells provided the Notch ligand Jagged1 to neighboring breast cancer stem cells, leading to Notch1-dependent upregulation of Zeb1.
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Jiang, H., Zhou, C., Zhang, Z., Wang, Q., Wei, H., Shi, W., Li, J., Wang, Z., Ou, Y., Wang, W., Wang, H., Zhang, Q., Sun, W., Sun, P., & Yang, S. (2020). Jagged1-Notch1-deployed tumor perivascular niche promotes breast cancer stem cell phenotype through Zeb1. Nature Communications, 11(1), 5129. https://doi.org/10.1038/s41467-020-18860-4 Cite
Researchers investigated the role of TAp63α in colorectal cancer stem cells and the effects of sulforaphane on TAp63α. They found that TAp63α was upregulated in spheres with stem cell properties compared to the parental cells.
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Investigators analyzed the levels of mRNA transcripts in serum‐starved primary WT and KO mouse hepatocytes using RNA sequencing data, and found that cyclic AMP response element‐binding protein target genes were downregulated.
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Single-cell sequencing data from seven surgical specimens of glioblastoma patients and patient-derived glioma stem cells co-cultured with peripheral leukocytes were used for the analysis.
[Frontiers in Immunology]
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Investigators evaluated the potential anti-tumor effect of Tideglusib, an irreversible glycogen synthase kinase (GSK)-3β inhibitor drug, on three human neuroblastoma cell lines, SK-N-SH, SH-SY5Y, and IMR-32.
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Bahmad, H. F., Chalhoub, R. M., Harati, H., Bou-Gharios, J., Assi, S., Ballout, F., Monzer, A., Msheik, H., Araji, T., Elajami, M. K., Ghanem, P., Chamaa, F., Kadara, H., Abou-Antoun, T., Daoud, G., Fares, Y., & Abou-Kheir, W. (2020). Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3β. Pharmacological Reports. https://doi.org/10.1007/s43440-020-00162-7 Cite
TGFβ1 rich secretome from Helicobacter pylori-reprogrammed fibroblasts prompted phenotypic plasticity and epithelial–mesenchymal transition (EMT) of gastric epithelium, inducing pro-neoplastic expansion of post-EMT cells in the presence of low TGFβR1 and TGFβR2 activity.
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Krzysiek-Maczka, G., Targosz, A., Szczyrk, U., Wrobel, T., Strzalka, M., Brzozowski, T., Czyz, J., & Ptak-Belowska, A. (2020). Long-Term Helicobacter pylori Infection Switches Gastric Epithelium Reprogramming Towards Cancer Stem Cell-Related Differentiation Program in Hp-Activated Gastric Fibroblast-TGFβ Dependent Manner. Microorganisms, 8(10), 1519. https://doi.org/10.3390/microorganisms8101519 Cite
Scientists defined an extended role for an effective immune response, not just in direct killing of tumor cells, but in widescale remodelling of the tumor microenvironment to favor loss of ECM, elimination of cancer stem cells, and propagation of adaptive immunity.
[Cancer Immunology Research]
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Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite