Integrative Cancer Care

Do not get so fat. Excessive adipose tissue can induce cancer.

Fibroblast growth factor receptor is a mechanistic link between visceral adiposity and cancer

Oncogene advance online publication 7 August 2017

Abstract

Epidemiological evidence implicates excess adipose tissue in increasing cancer risk. Despite a steeply rising global prevalence of obesity, how adiposity contributes to transformation (stage a non-tumorigenic cell undergoes to become malignant) is unknown. To determine the factors in adipose tissue that stimulate transformation, we used a novel ex vivosystem of visceral adipose tissue (VAT)-condition medium-stimulated epithelial cell growth in soft agar. To extend this system in vivo, we used a murine lipectomy model of ultraviolet light B-induced, VAT-promoted skin tumor formation. We found that VAT from mice and obese human donors stimulated growth in soft agar of non-tumorigenic epithelial cells. The difference in VAT activity was associated with fibroblast growth factor-2 (FGF2) levels. Moreover, human and mouse VAT failed to stimulate growth in soft of agar in cells deficient in FGFR-1 (FGF2 receptor). We also demonstrated that circulating levels of FGF2 were associated with non-melanoma tumor formation in vivo. These data implicate FGF2 as a major factor VAT releases to transform epithelial cells—a novel, potential pathway of VAT-enhanced tumorigenesis. Strategies designed to deplete VAT stores of FGF2 or inhibit FGFR-1 in abdominally obese individuals may be important cancer prevention strategies as well as adjuvant therapies for improving outcomes.

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Integrative Cancer Care

You are quite “Lucky”, if you are not a cancer patient.

Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

Science  24 Mar 2017:
Vol. 355, Issue 6331, pp. 1330-1334

Fig 3. 유전적 요인(Hereditary), 환경적 요인(Environmental)에 비해서, DNA replication에 의한 driver mutation (Replicative)의 비율이 여러 암종을 통틀어서도 매우 높다.jpg

Cancer and the unavoidable R factor

Most textbooks attribute cancer-causing mutations to two major sources: inherited and environmental factors. A recent study highlighted the prominent role in cancer of replicative (R) mutations that arise from a third source: unavoidable errors associated with DNA replication. Tomasetti et al. developed a method for determining the proportions of cancer-causing mutations that result from inherited, environmental, and replicative factors (see the Perspective by Nowak and Waclaw). They found that a substantial fraction of cancer driver gene mutations are indeed due to replicative factors. The results are consistent with epidemiological estimates of the fraction of preventable cancers.

Science, this issue p. 1330; see also p. 1266

Abstract

Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.

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