Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery

Matilde Todaro, Melania Lo Iacono, Miriam Gaggianesi, Veronica Veschi, Alice Turdo, Giorgio Stassi, Laura Rosa Mangiapane, Maria Rita Bongiorno, Simone Di Franco, Salvatore Vieni, Eliana Gulotta, Annalisa Nicotra, Eliana Gulotta, Sander Van Hooff, Lorenzo Colarossi, Federica Martorana, Vincenzo Luca Lentini, Gianmarco Motta, Emanuele Martorana, Lorenzo MemeoGiorgio Giannone, Marzia Mare, Paolo Vigneri, Dario Giuffrida, Jan Paul Medema, Micol Eleonora Fiori, Ruggero De Maria, Vincenzo Luca Lentini

Risultato della ricerca: Articlepeer review

10 Citazioni (Scopus)

Abstract

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored. Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease
Lingua originaleEnglish
Numero di pagine16
RivistaNature Communications
Volume12
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1300???
  • ???subjectarea.asjc.3100.3100???

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