Differentiated Human Colorectal Cancer Cells Protect Tumor-Initiating Cells From Irinotecan

Emmink, Benjamin L.; Houdt, Winan J. van; Vries, Robert G.J.; Hoogwater, Frederik J.H.; Govaert, Klaas M.; Verheem, André; Nijkamp, Maarten W.; Steller, Ernst J.A.; Jiménez, Connie R.; Clevers, Hans; Rinkes, Inne H.M. Borel; Kranenburg, Onno

doi:10.1053/j.gastro.2011.03.052

Cited by 81 publications

(85 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In GBM, the minor subset of glioma cells that carry mutated (i.e., constitutively activated) EGFR behaves like CSCs and preferentially expresses IL-6 and/or LIF (leukemia inhibitory factor), which activate gp130 and wildtype EGFR in the majority of (non-stem) glioma cells and promote their CSC properties [68]. Vice versa, nonCSCs in colon cancers can protect CSCs from the toxicity of chemotherapeutic drugs [148]. These discussions illustrate the potential benefit of combinatorial targeting of both tumor-initiating and differentiated tumor cells [149].…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Understanding cancer stem cell heterogeneity and plasticity

2012

View full text Add to dashboard Cite

Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

show abstract

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Understanding cancer stem cell heterogeneity and plasticity

2012

View full text Add to dashboard Cite

show abstract

“…In GBM, GSCs that express high levels of mutated EGFR produce interleukin-6 and leukemia inhibitory factor, which activate gp130 and wild-type EGFR in the adjacent non-GSCs within glioma tissue (43). Conversely, non-CSCs in colon cancers protect CSCs from the toxic effects of chemotherapeutic drugs (62). Taken together, these observations highlight the benefit of targeting undifferentiated CSCs as well as differentiated non-CSCs.…”

Section: Resultsmentioning

confidence: 99%

Targeted therapy against cancer stem cells

Yang

Rycaj

2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Research into cancer stem cells (CSCs), which have the ability to self-renew and give rise to more mature (differentiated) cancer cells, and which may be the cells responsible for the overall organization of a tumor, has progressed rapidly and concomitantly with recent advances in studies of normal tissue stem cells. CSCs have been reported in a wide spectrum of human tumors. Like normal tissue stem cells, CSCs similarly exhibit significant phenotypic and functional heterogeneity. The ability of CSCs to self-renew results in the immortality of malignant cells at the population level, whereas the ability of CSCs to differentiate, either fully or partially, generates the cellular hierarchy and heterogeneity commonly observed in solid tumors. CSCs also appear to have maximized their pro-survival mechanisms leading to their relative resistance to anti-cancer therapies and subsequent relapse. Studies in animal models of human cancers have also provided insight into the heterogeneity and characteristics of CSCs, helping to establish a platform for the development of novel targeted therapies against specific CSCs. In the present study, we briefly review the most recent progress in dissecting CSC heterogeneity and targeting CSCs in various human tumor systems. We also highlight a few examples of CSC-targeted drug development and clinical trials, with the ultimate aim of developing more effective therapeutic regimens that are capable of preventing tumor recurrence and metastasis. IntroductionThe etiology of cancer development and the molecular mechanisms underlying conventional therapy-resistant progression, metastasis and recurrence are poorly understood, resulting in numerous patients who still fail therapy. Cancer is recognized as a heterogeneous disease, an intrinsic attribute that contributes to therapy failure. Emerging evidence from a number of tumor systems has revealed the existence of distinct subpopulations of stem-like cancer cells, termed cancer stem cells (CSCs), that possess clonal long-term repopulation and self-renewal capacities. Theories suggest that both genetic and CSC models of cancer contribute to this tumor heterogeneity. With stemness as a guiding principle, data generated from advanced genome sequencing, epigenetics and the influences of non-tumor cell elements in the tumor microenvironment could potentially be combined in order to reveal the underlying mechanisms of tumor heterogeneity (1). As a fraction of this heterogeneous population, CSCs are inherently resistant to cytotoxic chemotherapy and radiation, and evidence has linked stemness to prognosis and therapy failure (2). This suggests that specifically identifying how CSC involvement is linked to tumor initiation, progression, metastasis and therapy resistance may lead to a more perceptive approach of developing therapeutics to target this cell population. Despite the vast complexity observed within a tumor, there are fundamental attributes of CSCs that may be exploited in drug development. A number of potential CSC therapeutic...

show abstract

“…They disrupted the Abcb1a gene and found decreased intestinal polyp and tumor incidence compared with Abcb1a wild-type mice, suggesting that P-gpmediated protection from xenotoxins allows epithelial cells with strong driver mutations to survive and progress into malignant tumors. This protective effect of P-gp may be specific for mice, as tumor-initiating cells of human colorectal tumors do not appear to be protected by ABCB1 (4). In contrast, Gupta and colleagues (5) found loss of ABCG2 protein and mRNA expression in human colorectal and cervical cancers and they hypothesized that increased exposure to carcinogenic genotoxins in premalignant cells might enhance tumor evolution through stimulated mutagenesis.…”

Section: And Colleagues (3) Reported In Heterozygous Apcmentioning

confidence: 99%

Lack of ABCG2 Shortens Latency of BRCA1-Deficient Mammary Tumors and This Is Not Affected by Genistein or Resveratrol

Zander¹,

Kersbergen²,

Sol³

et al. 2012

Cancer Prevention Research

View full text Add to dashboard Cite

In addition to their role in drug resistance, the ATP-binding cassette (ABC) transporters ABCG2 and ABCB1 have been suggested to protect cells from a broad range of substances that may foster tumorigenesis. Phytoestrogens or their metabolites are substrates of these transporters and the influence of these compounds on breast cancer development is controversial. Estrogen-like properties might accelerate tumorigenesis on the one hand, whereas their proposed health-protective properties might antagonize tumorigenesis on the other. To address this issue, we used a newer generation mouse model of BRCA1-mutated breast cancer and examined tumor latency in K14cre;Brca1

show abstract

Differentiated Human Colorectal Cancer Cells Protect Tumor-Initiating Cells From Irinotecan

Cited by 81 publications

References 37 publications

Understanding cancer stem cell heterogeneity and plasticity

Understanding cancer stem cell heterogeneity and plasticity

Targeted therapy against cancer stem cells

Lack of ABCG2 Shortens Latency of BRCA1-Deficient Mammary Tumors and This Is Not Affected by Genistein or Resveratrol

Contact Info

Product

Resources

About