Protective effects of eicosapentaenoic acid in adipocyte-breast cancer cell cross talk

Combined Effects of Eicosapentaenoic Acid and Adipocyte Renin–Angiotensin System Inhibition on Breast Cancer Cell Inflammation and Migration

“…The aim of the current study was to provide new insights into adipocyte-BC interaction through inhibition of RAS in adipocytes. We previously showed protective effects of n-3 PUFAs in adipocyte-BC cell interactions [27]. Moreover, we demonstrated that n-3 PUFAs reduce Agt secretion from adipocytes and reduce both systemic and adipose tissue inflammation [29].…”

“…We found a similar induced wound-healing capacity in MDA-MB-231 cells in response to human adipose CM. On the contrary, given the anti-inflammatory and antiproliferative effects of EPA on MDA-MB-231 cell motility [27] and the proposed similar effects for ACE-I, we combined them to identify their synergistic or additive effects in MDA-MB-231 TNBC. Surprisingly, both direct and CM-mediated EPA and ACE-I combination were ineffective in reducing TNBC cell motility compared with either EPA or ACE-I alone.…”

“…The BC cells were treated directly with the ACE inhibitor CAP (100 µm) with or without EPA (100 µm) combination for 48 h to identify their individual/combined effect in modulating BC cell metabolism ( Figure S1). The time and dose of our current treatments (CAP and EPA) were based on our previous work using EPA alone [27] or CAP alone (manuscript under review) against adipocyte-BC-cell interactions. CM experiments were performed between differentiated human adipocytes (HMSCs) and BC cells.…”

“…RAS can also be downregulated by anti-inflammatory dietary bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) [22], which we have also shown to reduce Agt secretion from adipocytes [23]. The dietary n-3 PUFAs eicosapentaenoic acid (EPA)-20:5n-3 and docosahexaenoic acid (DHA)-22:5n-3 have potent anti-inflammatory properties that include reducing obesity-associated systemic and adipose tissue inflammation, thus alleviating TME formation in adipocyte-BC-cell crosstalk [24][25][26][27]. Therefore, given the promising anti-inflammatory and anticancer properties of ACE-I and EPA, we hypothesized that ACE-I (captopril (CAP)) and EPA alone or in combination would attenuate BC cell inflammation and migration, in part through inhibition of adipocyte RAS.…”

Tumor Microenvironment Uses a Reversible Reprogramming of Mesenchymal Stromal Cells to Mediate Pro-tumorigenic Effects

“…However, MSCs also reside in the tumor microenvironment, where they were reported to promote pivotal tumorigenic processes such as: (i) malignant transformation; (ii) cancer cell maintenance and stemness; (iii) cancer stem cell niche formation, including angiogenesis and neovascularization; (iv) metastasis formation; and (v) resistance to anticancer drugs [for review see Seke Etet et al (2013) , Nwabo Kamdje et al (2014) , Atiya et al (2020) , Osman et al (2020) ]. On the other hand, MSC-derived stromal cells restraining cancer growth have been reported in the tumor microenvironment ( Bu et al, 2019 ; Mizutani et al, 2019 ; Tew et al, 2019 ) and growing evidence supports that the pro-tumorigenic effects of MSCs emerge from cell reprogramming by the tumor microenvironment ( Coffman et al, 2019 ; Mandal et al, 2019 ; Al-Jawadi et al, 2020 ; Boada et al, 2020 ). Herein, we provide an overview and discuss emerging data supporting MSC reprogramming by the tumor microenvironment and recent reports supporting the existence of stromal cells restraining cancer growth in the tumor microenvironment.…”