Dataset Information

A possible explanation for the variable frequencies of cancer stem cells in tumors.

ABSTRACT: A controversy surrounds the frequency of cancer stem cells (CSCs) in solid tumors. Initial studies indicated that these cells had a frequency ranging from 0.0001 to 0.1% of the total cells. Recent studies have shown that this does not always seem to be the case. Some of these studies have indicated a frequency of [Formula: see text]. In this paper we propose a stochastic model that is able to capture this potential variability in the frequency of CSCs among the various type of tumors. Considerations regarding the heterogeneity of the tumor cells and its consequences are included. Possible effects on conventional treatments in clinical practice are also described. The model results suggest that traditional attempts to combat cancer cells with rapid cycling can be very stimulating for the cancer stem cell populations.

SUBMITTER: dos Santos RV

PROVIDER: S-EPMC3737222 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A possible explanation for the variable frequencies of cancer stem cells in tumors.

dos Santos Renato Vieira RV da Silva Linaena Méricy LM

PloS one 20130807 8

A controversy surrounds the frequency of cancer stem cells (CSCs) in solid tumors. Initial studies indicated that these cells had a frequency ranging from 0.0001 to 0.1% of the total cells. Recent studies have shown that this does not always seem to be the case. Some of these studies have indicated a frequency of [Formula: see text]. In this paper we propose a stochastic model that is able to capture this potential variability in the frequency of CSCs among the various type of tumors. Considerat ...[more]

PMID: 23950884

Similar Datasets

Project description:BackgroundPatients generally die of cancer after the failure of current therapies to eliminate residual disease. A subpopulation of tumor cells, termed cancer stem cells (CSC), appears uniquely able to fuel the growth of phenotypically and histologically diverse tumors. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. The subpopulation of human colorectal tumor cells with an ESA(+)CD44(+) phenotype are uniquely responsible for tumorigenesis and have the capacity to generate heterogeneous tumors in a xenograft setting (i.e. CoCSC). We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.Methods and findingsXenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. Moreover, the inherent ability of residual CoCSC to generate tumors appears preserved. Aldehyde dehydrogenase 1 gene expression and enzymatic activity are elevated in CoCSC and using an in vitro culture system that maintains CoCSC as demonstrated by serial transplants and lentiviral marking of single cell-derived clones, we further show that ALDH1 enzymatic activity is a major mediator of resistance to cyclophosphamide: a classical chemotherapeutic agent.ConclusionsCoCSC are enriched in colon tumors following chemotherapy and remain capable of rapidly regenerating tumors from which they originated. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy.

Dataset Information

A possible explanation for the variable frequencies of cancer stem cells in tumors.

Publications

A possible explanation for the variable frequencies of cancer stem cells in tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets