Renin angiotensin system inhibition attenuates adipocyte-breast cancer cell interactions

Fahmida Rasha, Latha Ramalingam, Kalhara Menikdiwela, Arelys Hernandez, Hanna Moussa, Lauren Gollahon, Rakhshanda Layeequr Rahman, Naima Moustaid-Moussa

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity is a significant breast cancer (BC) risk factor and is associated with 20–40% increased risk in obese post-menopausal women compared to their lean counterparts. Several obesity-related metabolic dysregulations have been linked to BC risk, including overactivation of the renin-angiotensin system (RAS). Currently, RAS inhibitors including angiotensin converting enzyme inhibitor (ACEi) and AT1 receptor blockers (ARBs), are used as safe and effective anti-hypertensive therapies in BC patients. However, it is uncertain how inhibition of RAS in adipose tissue impacts obesity-BC crosstalk. We hypothesized that adipose RAS inhibition will reduce BC cell motility and inflammation. We determined (1) the direct effects of Ang II, ACEi (captopril; Cap) or ARB (telmisartan; Tel) on receptor positive MCF-7 and receptor triple negative MDA-MB-231 cells; and (2) the effects of conditioned media (CM) from human mesenchymal stem cells differentiated into adipocytes, which were pretreated with RAS inhibitors, on BC cells. We demonstrated that direct treatments of BC cells with Ang II, Cap or Tel did not alter inflammatory cytokines in either BC cell line. However, CM from Ang II-pretreated adipocytes significantly increased secretion of pro-inflammatory markers at protein level. RAS inhibitors reduced their secretion in MDA-MB-231, but not in MCF-7 cells. Additionally, CM from adipocytes treated with RAS inhibitors significantly reduced markers of inflammation, fat synthesis, and angiogenesis in both BC cell lines. Furthermore, CM from ACEi pretreated adipocytes reduced cell motility in both BC cell lines. Findings from our study indicate an important role of adipose RAS inhibition in adipocyte and BC cell crosstalk.

Original languageEnglish
Article number112114
JournalExperimental Cell Research
Volume394
Issue number1
DOIs
StatePublished - Sep 1 2020

Keywords

  • Adipocytes
  • Breast cancer
  • Inflammation
  • Obesity
  • Renin-angiotensin system

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