Beige adipocytes contribute to breast cancer progression

Abstract

Adipocytes are the main stromal cells in the mammary microenvironment, and crosstalk between adipocytes and breast cancer cells may play a critical and important role in cancer maintenance and progression. Tumor-induced differentiation to beige/brown adipose tissue is an important contribution to the hypermetabolic state of breast cancer. However, the effect of epithelial cell-beige adipocyte communication on tumor progression remains unclear. To contribute to the understanding of this phenomenon, we characterized components present in conditioned media (CM) from beige adipocytes (BAs) or white adipocytes (WAs), and evaluated the effects of BA-and WA-CM on both adhesion and migration of tumor (LM3, 4T1 and MC4-L1) and non-tumor (NMuMG) mouse mammary epithelial cell lines. Additionally, we analyzed the expression of ObR, CD44, vimentin, MMP-9, MCT1 and LDH in tumor and non-tumor mouse mammary epithelial cell lines incubated with BA-CM, WA-CM or Ctrol-CM (control conditioned media). 3T3-L1 preadipocytes differentiated into beige adipocytes upon PPARγ activation (rosiglitazone) displaying characteristics that morphologically resembled brown/beige adipocytes. Levels of UCP1, CIDEA, GLUT4, leptin, MCT4 and FABP4 were increased, while adiponectin, caveolin 1 and perilipin 1 levels were decreased in BAs with respect to WAs. Tumor cell lines revealed lower cell adhesion and increased cell migration after incubation with BA-and WA-CM vs. Ctrol-CM. ObR and MMP-9 in MC4-L1 cells were significantly increased after incubation with BA-CM vs. WA-and Ctrol-CM. In addition, MC4-L1 and LM3 cells significantly increased their migration in the presence of BAs, suggesting that new signals originating from the crosstalk between BAs and tumor cells, could be responsible for this change. Our results indicate that beige adipocytes are able to regulate the behavior of both tumor and non-tumor mouse mammary epithelial cells, favoring tumor progression.

Perirenal White Adipose Tissue Browning and Epithelial-Mesenchymal Transition, Contributes To Tumor Development in Kidney Cancer

“…Adipocytes are the main stromal cells in the mammary microenvironment, and crosstalk between adipocytes and cancer cells may play a critical and important role in cancer maintenance and progression. Tumor induced differentiation to beige/brown adipose tissue is an important contribution to the hypermetabolic state of breast [20] and prostate [7] cancer, but still the bibliography says nothing about browning and kidney cancer. And, the effect of epithelial cell-beige adipocyte communication on tumor progression remains unclear.…”

“…Both due to phenotypic modi cations of the peritumoral adipose tissue, and due to changes in the expression of genes involved in the browning process [17-19;7;20]. Gantov et al recently demonstrated that beige adipocytes favor tumor progression of mouse mammary epithelial cell lines, both tumor and non-tumor [20]. Our group recently demonstrated that renal peritumoral AT (hRAT) favors tumor progression through soluble factors that it secretes into the microenvironment, unlike normal renal adipose tissue (hRAN).…”

“…[5]. Tumor-induced differentiation to beige/brown adipose tissue is an important contribution to the hypermetabolic state of breast cancer [20]. Therefore, we evaluated changes in the expression of WAT and BAT/beige markers in hRAN and hRAT by different methods.…”

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

“…The reciprocal interaction of the adipose microenvironment and breast cancer tissue is a critical factor in promoting cancer cell migration [ 50 ]. Experimental results showed that adipose cells led to a decrease in the viability of myoepithelial cells (MECs), which are known as tumor suppressor cells that block the transition from ductal carcinoma in situ to invasive carcinoma.…”

Differential Gene -Based Predictors of Neoadjuvant Chemotherapy Efficacy in Breast Cancer

“…CIDEA and ADIPOQ are highly expressed in breast tissue and adipose tissue, and both of them could promote apoptosis of tumour cell lines and might inhibit tumour growth [26]. However, research supports that CIDEA participates in the interaction of tumour and nontumour mouse mammary epithelial cells, ultimately accelerating tumour progression [27]. In addition, a relevant point worth mentioning is that the adiponectin-AdipoR1 axis was defined as a predictor of tyrosine kinase inhibitor resistance in metastatic renal cell carcinoma [28]…”