Not all cancer cells are born equal. While the great majority of the cells that make up tumours are destined to differentiate, albeit aberrantly, and eventually stop dividing, a handful of cancer cells appear to possess limitless replicative potential. This review presents compelling evidence to suggest that the bulk of malignant cells of most cancers are generated by a rare fraction of stem cell-like cancer cells. These cells, dubbed cancer stem cells, are phenotypically similar to the normal stem cells of the corresponding tissue of origin, but they exhibit dysfunctional patterns of self-renewal and differentiation. Cancer stem cells that are capable of recapitulating brain tumours as xenografts in mice are characterised by defined stem cell markers. These brain tumour stem cells demonstrate enhanced chemoresistance and radioresistance mechanisms compared to non-stem cells in the heterogeneous tumour, which suggest that they may be the likely candidates for tumour progression and recurrence. Indeed, recent work has shown that such aberrant signalling pathways may be targeted in novel anti-cancer therapeutic strategies. The stem cell concept of tumour progression prompts immediate attention to a new paradigm in cancer research with a focus on this minority subset of cells, and the design of novel therapeutic strategies to target these cells that are insignificant within the population of tumour cells, but that are in fact the relevant cells to be destroyed.
Cell Transformation, Neoplastic ; Glioma ; pathology ; radiotherapy ; Humans ; Models, Biological ; Neoplastic Stem Cells ; drug effects ; pathology ; Singapore

Adenoma, Pleomorphic/surgery* ; Brain/pathology* ; Cell Transformation, Neoplastic/pathology* ; Humans ; Lung/pathology* ; Salivary Gland Neoplasms/pathology*

Adenocarcinoma, Clear Cell/pathology* ; Carcinoma in Situ ; Cell Transformation, Neoplastic ; China ; Endometriosis/pathology* ; Female ; Humans

Tumor microenvironment is composed of mesenchymal cells and extracellular matrix components, which plays an important role in the growth, invasion and metastasis of tumor cells. Characteristic changes of stroma are usually accompanied with the malignant transformation of epithelial cells even ahead. The key component in the process-activated fibroblasts, also known as myofibroblasts, or cancer-associated fibroblasts (CAF), is the most abundant cells in tumor stroma. They promote the malignant transformation of epithelial cells through cell-cell communication via various soluble factors. This article reviews cancer-associated fibroblasts and their role in tumor development.
Cell Communication ; Cell Transformation, Neoplastic ; pathology ; Disease Progression ; Epithelial Cells ; pathology ; Fibroblasts ; pathology ; Humans ; Myoblasts ; pathology ; Neoplasms ; pathology ; physiopathology

Cancer stem cells are defined as rare cells in cancer tissues with indefinite potential for self-renewal that drives tumorigenesis. It was first extensively documented for leukaemia and multiple myeloma. It has also been found in solid cancers such as human breast cancer and nervous system tumors. Studies of cancer stem cell biology and mechanisms of tumorigenesis are lending insight into the origins of cancer and will ultimately yield new approaches to fight cancer.
Animals ; Cell Transformation, Neoplastic ; Humans ; Mice ; Neoplasms ; pathology ; therapy ; Neoplastic Stem Cells ; cytology ; Tumor Stem Cell Assay ; methods

Animals ; Brain Neoplasms ; genetics ; pathology ; Cell Differentiation ; Cell Transformation, Neoplastic ; genetics ; Glioma ; genetics ; pathology ; Humans ; Neoplastic Stem Cells ; pathology ; Neural Stem Cells ; pathology ; Neuroglia ; pathology ; Neurons ; pathology

OBJECTIVETo study the biological effects of nickel-refining dust.

METHODSThe cell phagocytosis, transformation activity, and cytotoxicity of the mouse NIH3T3 cells treated with nickel-refining dusts from two nickel-refining factories in China were observed, and the risk of carcinogenicity was studied.

RESULTS(1) Two samples of nickel-refining dusts could be phagocytosed by mouse NIH3T3 cells with different phagocytizing rates of 69.0% and 39.0% at 100.000 micro g/ml, and 78.0% and 47.0% at 200.000 micro g/ml respectively. The relative clone formation rates at 12.500 micro g/ml to 100.000 micro g/ml were 71.1% to 3.9% and 84.4% to 9.1%, respectively. The cytotoxicity expressed by clone formation rate was similar to that of Ni(2)O(3), but higher than that of TiO(2) and lower than the positive control of N-methyl-N'-nitro-N-nitroso-guanidine (MNNG). (2) MNNG, Ni(2)O(3) and the two samples of nickel-refining dusts could induce morphological transformation in NIH3T3 cells. The transformation rate at 12.500 micro g/ml to 50.000 micro g/ml were 1.9% to 3.6% and 0.9% to 2.5% respectively in a dose-dependent manner. (3) The NIH3T3 cells treated by MNNG and nickel-refining dusts could induce Con A agglutination, and may form as clone in soft agar. This finding proved the reliability of the transformed clone.

CONCLUSIONSThe present study for the first time demonstrate that nickel-refining dusts have cell transformation activity. The findings provide a new experimental evidence for the carcinogenic risk of nickel-refining dusts, and for the aetiology of lung cancer in nickel-refining workers.

Adult ; Cell Transformation, Neoplastic ; Craniopharyngioma ; pathology ; surgery ; Humans ; Male ; Neurosurgery ; Young Adult

Adolescent ; Carcinoma, Squamous Cell ; pathology ; surgery ; Cell Transformation, Neoplastic ; Craniopharyngioma ; pathology ; surgery ; Humans ; Male ; Pituitary Neoplasms ; pathology ; surgery

Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation.
Aneuploidy ; Animals ; Cell Differentiation ; Cell Transformation, Neoplastic ; genetics ; pathology ; Humans ; Neoplasms ; genetics ; pathology ; Pluripotent Stem Cells ; pathology