Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells

Ruggero De Maria Marchiano, Monica Bartucci, Susanne Svensson, Lucia Ricci-Vitiani, Rosanna Dattilo, Mauro Biffoni, Michele Signore, Rita Ferla, Eva Surmacz

Risultato della ricerca: Contributo in rivistaArticolo in rivista

44 Citazioni (Scopus)

Abstract

The incidence of colon cancer has increased in developed countries, possibly due to sedentary lifestyle and high caloric diet. Experimental and epidemiological evidence suggests a link between colon cancer development and adipose tissue-derived circulating hormones. Leptin, a pluripotent cytokine secreted by adipocytes, is a key regulator of appetite and energy balance acting in the brain. On the other hand, leptin also controls many physiological and pathological processes in peripheral organs. Recent studies in colon cancer cell lines and human tumors suggested that leptin and its receptor (ObR) are implicated in colon carcinogenesis, and may serve as new biomarkers and pharmacological targets. Here, we explored, for the first time, whether leptin can affect the biology of colorectal tumor stem cells (CTSCs). We found that our previously established and characterized CTSC clones express ObR and respond to leptin with cell proliferation, activation of the extracellular signal-related kinase (ERK)1/2 and AKT signaling pathways, enhanced growth in soft agar, and improved sphere formation associated with E-cadherin overexpression. Moreover, leptin counteracted cytotoxic effects of 5-fluorouracil, a common colon cancer therapeutic agent. These results suggest that obesity and increased leptin levels might promote colorectal cancer by increasing growth and survival of CTSCs. © 2010 Society for Endocrinology.
Lingua originaleEnglish
pagine (da-a)823-833
Numero di pagine11
RivistaEndocrine-Related Cancer
Volume17
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Antimetabolites, Antineoplastic
  • Apoptosis
  • Biomarkers, Tumor
  • Blotting, Western
  • Cancer Research
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Colony-Forming Units Assay
  • Colorectal Neoplasms
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Fluorouracil
  • Humans
  • Leptin
  • Neoplastic Stem Cells
  • Obesity
  • Oncology
  • Receptors, Leptin
  • Signal Transduction

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