Regeneration: The origin of cancer or a possible cure?

Oviedo, Néstor J.; Beane, Wendy S.

doi:10.1016/j.semcdb.2009.04.005

Cited by 126 publications

(107 citation statements)

References 56 publications

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“…One of the suggested mechanisms to explain the initiation of colonic injuryinduced cancer is repetitive epithelial cell destruction and subsequent regeneration, resulting in enhanced mutation (33,34). To investigate this possibility, we analyzed the proliferation and survival of intestinal epithelial cells at day 15 of the CAC regimen in Casp1 −/− and WT mice.…”

Section: Enhanced Colon Epithelial and Tumor Cell Proliferation In Casp1mentioning

confidence: 99%

Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4

Elinav²,

Huber³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

407

366

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Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association is currently unknown. The inflammasome, a multiprotein complex formed by NOD-like receptor (NLR) family members, has recently been shown to orchestrate multiple innate and adaptive immune responses, yet its potential role in inflammation-induced cancer has been little studied. Using the azoxymethane and dextran sodium sulfate colitis-associated colorectal cancer model, we show that caspase-1-deficient (Casp1 −/− ) mice have enhanced tumor formation. Surprisingly, the role of caspase-1 in tumorigenesis was not through regulation of colonic inflammation, but rather through regulation of colonic epithelial cell proliferation and apoptosis. Consequently, caspase-1-deficient mice demonstrate increased colonic epithelial cell proliferation in early stages of injury-induced tumor formation and reduced apoptosis in advanced tumors. We suggest a model in which the NLRC4 inflammasome is central to colonic inflammation-induced tumor formation through regulation of epithelial cell response to injury.colon cancer | inflammation-induced colorectal cancer | NLR family, pyrin domain containing 3

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Section: Enhanced Colon Epithelial and Tumor Cell Proliferation In Casp1mentioning

confidence: 99%

Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4

Elinav²,

Huber³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

407

366

View full text Add to dashboard Cite

show abstract

“…These findings suggest that regenerating tissues can resist or suppress carcinogen-induced malignant transformation and/or propagation of tumor cells within them. Although there is some evidence that urodeles may have a lower incidence of cancer than adult anuran amphibians (Anver, 1992), the ability to enforce (albeit abnormal) tissue morphogenesis over unrestrained proliferation and tumor formation seems to be a specific property of the actively regenerating tissue and the regeneration microenvironment, rather than a general property of the organism as a whole, which is susceptible (Braun, 1965;Zilakos et al, 1996;Oviedo and Beane, 2009). Urodeles, in contrast to zebrafish, have not yet been used as a genetic experimental organism for studying cancer.…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressors: enhancers or suppressors of regeneration?

Pomerantz

Blau

2013

Development

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SummaryTumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine.

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“…This is especially useful when studying the effect of carcinogenic compounds. As to cancer cells that do not have the capacity to terminate proliferation, regenerative tissue is able to control and end proliferation (Oviedo and Beane, 2009). Therefore, studying stem cells and their underlying mechanisms under influence of external stressors can provide a better understanding of the basic biology of stress and repair responses.…”

Section: Introductionmentioning

confidence: 99%

Physiological and molecular characterisation of cadmium stress in Schmidtea mediterranea

Plusquin

Stevens²,

Belleghem³

et al. 2012

Int. J. Dev. Biol.

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The planarian Schmidtea mediterranea is a well-studied model organism for developmental research, because of its stem cell system. This characteristic also provides a unique opportunity to study stress management and the effect of stress on stem cells. In this study, we characterised the stress signature at different levels of biological organization. The carcinogenic metal cadmium was used as a model chemical stressor. We focused on stem cell activity and its interaction with other known stress parameters. Here, we have found that S. mediterranea is able to cope with high internal levels of cadmium. At endpoints such as size and mobility, cadmium-related stress effects were detected but all of these responses were transient. Correspondingly, cadmium exposure led to an elevated mitotic activity of the neoblasts, at the same time points when the other responses disappeared. At the molecular level, we observed redox-related responses that can be linked with both repair as well as proliferation mechanisms. Together, our results suggest that these animals have a high plasticity. The induction of stem cell activity may underlie this 'restoring' effect, although a carcinogenic outcome after longer exposure times cannot be excluded.

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Regeneration: The origin of cancer or a possible cure?

Cited by 126 publications

References 56 publications

Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4

Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4

Tumor suppressors: enhancers or suppressors of regeneration?

Physiological and molecular characterisation of cadmium stress in Schmidtea mediterranea

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