As obesity negatively impacts cancer survival, the main goal of our group is to characterize the role of tumor-surrounding adipocytes in cancer progression and the molecular mechanisms involved in both lean and obese conditions. Our team has been the first to define the specific phenotype of adipocytes within the tumor microenvironment, cells that we name Cancer-Associated Adipocytes.
Growing evidence indicates that obesity is associated with increased cancer risk and negatively impacts cancer recurrence and survival. Adipose tissue (AT) is frequently found at close proximity to invasive primary solid tumours including breast and prostate cancer as well as in bone metastatic sites. Main function of adipocytes, the metabolically active cells of AT, is to store lipids and to deliver them, when needed, to energy demanding tissues. Adipocytes are also active endocrine cells that secrete a large variety of molecules including growth factors, chemokines and pro-inflammatory molecules.
Although AT share common features, each fat depot exhibits metabolic and secretory specificities. Thus, the use of human AT close to each type of tumor is key to the relevance of our results. The strong collaboration that we established since several years with clinicians allow us to work with human fat depots (mammary AT, periprostatic AT, bone-marrow AT). Some of the clinicians are members of the team and we welcome each year medical residents under training.
We have demonstrated that tumor-surrounding adipocytes promote aggressiveness by secreting soluble factors such as chemokines, pro-inflammatory cytokines and by modulating tumor cell metabolism One of the most specific and emerging mechanism regarding the role of mature adipocytes in the tumor microenvironment involves the ability of cancer cells to advantageously exploit the nourishing role of adipocytes. At primary tumor sites, tumor cells induce lipolysis in adipocytes leading to the release free fatty acid (FFA) or contained in extra-cellular-vesicles that are taken up by tumor cells. These FFA trigger a complex metabolic remodeling in cancer cells increasing their survival, invasive and metastatic abilities as well as resistance to treatment.
The team possesses national and international recognition as assessed by our 5 highly cited papers (Top 1 % Web of Science) in the field of adipose tissue and cancer (Dirat et al, Cancer Research, 2011 ; Bochet et al, Cancer Research, 2013 ; Lazar et al, Cancer Research, 2016 ; Laurent et al, Nature Communications, 2016 ; Wang et al, JCI Insight, 2017).
You can follow us on Twitter : @AdipoKToulouse
Our research topics
Main publications
- Attané C et al. (2020). Human bone marrow comprise a new adipocyte subtype with specific lipid metabolism. Cell Rep 30 :949
- Clement E et al. (2020). Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. EMBO J 39 : e102525.
- Lehuédé C et al. (2019) Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein (MVP). Breast Cancer Res. 21:7.
- Wang YY et al. (2017) Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight 2: e87489 (Top 1% Web of science).
- Lazar I et al. (2016) Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: a novel mechanism linking obesity and cancer. Cancer Res 76:4051 (Top 1% Web of Science)
- Laurent V et al. (2016) Periprostatic adipose tissue acts as a driving force for the progression of prostate cancer in obesity. Nature Commun 7:10230 (Top 1% Web of Science)
- Dirat B et al. (2011) Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res 71:2455 (Top 1% Web of Science).
Section of invasive breast tumor (mauve) coming into contact of mature adipocytes (white discs). The adipocytes at close proximity of cancer cells exhibit a decrease in size and lipid content (arrows).
Scientists
Research Assistants
Clinicians
Post-doctoral fellows
PhD students
Selected publications
This is short list of our main recent contributions to microenvironment, cancer and adipocytes research. Other papers and reviews are available through Pubmed.
Our latest reviews
- Attané C and Muller C. 2020. Drilling for Oil : Tumor-Surrounding Adipocytes Fueling Cancer. (2020). Trends in Cancer (Upon invitation) PMID : PMID: 32610069
- Estève et al, 2020. Periprostatic adipose tissue a heavy player in prostate cancer progression. Curr Opin Endocr Met Res Periprostatic adipose tissue: A heavy player in prostate cancer progression - ScienceDirect
- Lazar I*, Clement E* et al. 2018. A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite. Journal of Lipid Research. (Upon invitation)
- Fallone F et al. 2018. Breast cancer, obesity and adipose tissue: a high-risk combination. Med Sci (Paris). (in French, invited review)
- Attané C et al. 2018. Metabolic remodeling induced by adipocytes: a new Achilles' heel in invasive breast cancer? Curr Med Chem. (Upon invitation)
- Duong MN et al. 2017. The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance. Oncotarget.
- Clement E et al. 2017. Obesity and melanoma: could fat be fueling malignancy? Pigment Cell Melanoma Research. (Upon invitation)
- Laurent V et al. 2016. Dissemination of prostate cancer: a way paved of fat. Med Sci (Paris). (In French, invited review)
- Muller C et al. 2013. Unraveling the local influence of tumor-surrounding adipose tissue on tumor progression: cellular and molecular actors involved. In “Adipose Tissue and Cancer” (Editor M. Kolonin, Springer edition). (Invited contribution)
- Wang YY et al. 2012. Adipose tissue and epithelial cancer cells: a dangerous dynamic duo in breast cancer. Cancer Lett. (Upon invitation)
Role of tumor surrounding adipocytes in breast cancer progression: new links between obesity and cancer
- Lehuédé C*, Li X*, et al. 2019. Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein (MVP) Breast Cancer Res.
- Wang YY et al. 2017. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight. Top 1% Web of Science.
- Vaysse C et al. 2017. Inflammation of mammary adipose tissue occurs in overweight and obese patients exhibiting early-stage breast cancer. NPJ Breast Cancer.
- Bochet L et al. 2013. Adipocyte-Derived Fibroblasts promote tumor progression and contribute to desmoplastic reaction in breast cancer. Cancer Res. Top 1 % Web of science.
- Dirat B et al. 2011. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. National Press Release. Top 1 % Web of science.
Dissemination of prostate cancer: a way paved of fat
- Laurent V*, Toulet A*, et al. 2019. Periprostatic adipose tissue favors prostate cancer cell invasion in an obesity- dependent manner: role of oxidative stress. Mol Cancer Res.
- Laurent V et al. 2016. Periprostatic adipose tissue acts as a driving force for the local invasion of prostate cancer in obesity: role of the CCR3/CCL7 axis. Nat Commun. National Press Release CNRS, Highlighted in Nature Reviews Cancer and Nature Reviews Urology. Top 1% Web of Science.
A lipid transfer between adipocytes and tumor cells
- Lazar I*, Clement E*, et al. 2016. Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: a novel mechanism linking obesity and cancer. Cancer Res. National Press Release CNRS (in french), Highlighted in Nature Reviews Endocrinology. Top 1 % Web of science.
- Wang YY et al. 2017. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight. . Top 1% Web of Science
- Laurent V*, Toulet A*, et al. 2019. Periprostatic adipose tissue favors prostate cancer cell invasion in an obesity- dependent manner: role of oxidative stress. Mol Cancer Res.
- Clement E*, Lazar I*, et al. 2020. Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. EMBO J. PMID: 31919869
Role of bone-marrow adipocytes in bone metastasis
- Attané C*, Estève D*, et al. 2020. Human bone marrow comprise a new adipocyte subtype with specific lipid metabolism. Cell Rep PMID: 31995765 Highlighted in Nature Review Endocrinology : https://www.nature.com/articles/s41574-020-0333-0
Collaborations
Research Labs
- Dr Anne BOULOUMIE, Institute of Cardiovascular and Metabolic Diseases, TOULOUSE, France
- Dr Lionel LARUE, Institut Curie, PARIS, FRANCE
- Pr Olivier PIOT, Translational Biospectroscopy, REIMS, France
- Dr Marc POIROT, Cancer Research Institute, TOULOUSE, France
- Pr Philippe VALET and Dr Cedric DRAY, Institute RESTORE, TOULOUSE, France
Translational Programs
- For our prostate cancer topic, a strong collaboration has been established with the Urology Department (Pr Bernard MALAVAUD and Dr Mathieu ROUMIGUIÉ), the Radiology department (Dr Daniel PORTALES) and the Pathology Department (Dr Sarah Pericart) of the Toulouse Cancer Institute.
- For our breast cancer topic, a collaboration has been established with Pr Inger THUNE’s team (Division for Cancer, Surgery and Transplantation, Department of Cancer Treatment / Translational Research on Energetics and Cancer, Ulleval University Hospital, Oslo, Norway). We are involved in the clinical trial EBBA-II for the analysis of adipose tissue inflammation. We are also collaborating with the Breast Cancer Surgery Department (Pr Charlotte VAYSSE) as well as the Pathology Department (Dr Camille FRANCHET) of the Toulouse Cancer Institute.
- For our program on bone metastasis, a collaboration has been established with the Orthopedic surgery Department (Pr Nicolas REINA)
Funding
Our team is (or was) supported by several grants and fellowships from:
- Association pour la Recherche sur les Tumeurs Prostatiques
- Cancéropole Grand Sud-Ouest
- Fondation ARC pour la Recherche sur le Cancer
- Fondation de France
- Fondation pour la Recherche Médicale
- Fondation Toulouse Cancer-Santé
- French National Institute against Cancer (INCA PL-BIO2016 and 2020)
Our team was officially labelled by the Ligue Nationale contre le Cancer (2020-2025)
