Adipose-Induced Retroperitoneal Soft Tissue Sarcoma Tumorigenesis: A Potential Crosstalk between Sarcoma and Fat Cells
| Autor: | Alon Savidor, Yishai Levin, Shelly Loewenstein, Eran Nizri, Guy Lahat, Osnat Sher, Nir Lubezky, Meir Zemel, Joseph M. Klausner |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Leiomyosarcoma Proteomics Cancer Research Cell Survival Adipose tissue Tissue Culture Techniques 03 medical and health sciences Paracrine signalling Mice 0302 clinical medicine Adipokines Cell Movement Tandem Mass Spectrometry Cell Line Tumor Paracrine Communication medicine Adipocytes Tumor Microenvironment Animals Humans Retroperitoneal Neoplasms Molecular Biology Cell Proliferation Tube formation Tumor microenvironment Chemistry Soft tissue sarcoma Cell migration Neoplasms Experimental medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Culture Media Conditioned Cancer cell Cancer research Sarcoma Chromatography Liquid |
| Zdroj: | Molecular cancer research : MCR. 14(12) |
| ISSN: | 1557-3125 |
| Popis: | Previous data demonstrated that high retroperitoneal visceral fat content increases retroperitoneal soft-tissue sarcoma (RSTS) local recurrence and patients' mortality. Most RSTS tumors initiate and recur within visceral fat. The objective of the current study was to evaluate potential paracrine effects of visceral fat on RSTS. A xenograft model was used to evaluate in vivo effects of human visceral fat on STS growth. Tissue explants were prepared from visceral fat, and their conditioned medium (CM) was utilized for various in vitro experiments designed to evaluate growth, survival, migration, and invasion of STS and endothelial cells. Visceral fat–secreted protumorigenic factors were identified by mass spectrometry. The in vivo experiments demonstrated a significant increase in STS tumor growth rate when SK-LMS-1 leiomyosarcoma cells were colocalized with human visceral fat compared with subcutaneous injection of cancer cells only. The in vitro model demonstrated that visceral fat CM increased STS cellular growth and reduced doxorubicin-induced apoptosis. Visceral fat also enhanced STS cellular migration and invasion. In addition, visceral fat CM significantly increased endothelial cell tube formation, suggesting its role as a proangiogenic factor in the STS tumor microenvironment (TME). Using a robust proteomic approach, liquid chromatography and tandem mass spectrometry resolved various molecules within the visceral fat CM, of which a subset was associated with protumorigenic biologic processes. These results suggest that visceral fat directly interacts with STS cells by secreting specific adipokines into the TME, thus augmenting STS tumor cell proliferation and invasiveness. Fat-induced STS molecular deregulations should be studied to identify new potential prognostic and therapeutic targets. Implications: Visceral fat induces protumorigenic effects, in STS, through various secreted factors that should be investigated to improve our understanding of adipose–cancer cell interactions. Mol Cancer Res; 14(12); 1254–65. ©2016 AACR. |
| Databáze: | OpenAIRE |
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