Abstract
The cancer stem cell (CSC) concept proposes that cancer recurrence and metastasis are driven by CSCs. In this study, we investigated whether cells from colon adenocarcinoma (CA) with a CSC-like phenotype express renin-angiotensin system (RAS) components, and the effect of RAS inhibitors on CA-derived primary cell lines. Expression of RAS components was interrogated using immunohistochemical and immunofluorescence staining in 6 low-grade CA (LGCA) and 6 high-grade CA (HGCA) tissue samples and patient-matched normal colon samples. Primary cell lines derived from 4 HGCA tissues were treated with RAS inhibitors to investigate their effect on cellular metabolism, tumorsphere formation and transcription of pluripotency genes. Immunohistochemical and immunofluorescence staining showed expression of AT2R, ACE2, PRR, and cathepsins B and D by cells expressing pluripotency markers. β-blockers and AT2R antagonists reduced cellular metabolism, pluripotency marker expression, and tumorsphere-forming capacity of CA-derived primary cell lines. This study suggests that the RAS is active in CSC-like cells in CA, and further investigation is warranted to determine whether RAS inhibition is a viable method of targeting CSCs.
Highlights
The cancer stem cell (CSC) concept hypothesizes that tumor growth is driven by CSCs, a small subpopulation of cancer cells with stem cell characteristics [1,2,3,4]
angiotensinconverting enzyme (ACE) was detected by RT-qPCR in all low-grade CA (LGCA) and high-grade CA (HGCA) tissues and patient-matched normal colon (NC) tissues with variable relative abundances (Fig 1Q)
Colon adenocarcinoma cells modulated by renin-angiotensin system inhibitors staining of stemness-associated markers with RAS components was performed to investigate if these components were expressed by the NANOG+ colon adenocarcinoma (CA) CSC-like subpopulation on the tumor epithelium and by an OCT4+ cell subpopulation in the stroma of CA tissues
Summary
The cancer stem cell (CSC) concept hypothesizes that tumor growth is driven by CSCs, a small subpopulation of cancer cells with stem cell characteristics [1,2,3,4]. CSCs divide asymmetrically to produce identical CSCs, as well as progenitor cells–the transit amplifying cells of the colon [5,6,7]. CSCs have lost control of cellular homeostasis leading to dysregulated cellular replication and differentiation, resulting in uncontrolled growth and tumor formation [1,2,3, 8]. CSCs resist conventional therapies and are responsible for tumor recurrence and metastasis [1,2,3].
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