Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors

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.

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

“…In terms of pathological processes, CTSB related to arthritis and atherosclerotic vascular diseases 17 , and has also been confirmed to be involved in inflammatory brain diseases and brain aging 21 , memory and psychiatric disorders and neuronal cascade death response after cerebral infarction 22 . CTSB has been regarded as an important biomarker and potential therapeutic target for many cancers 15 , such as pancreatic cancer 23 , gastric cancer 24 , colon cancer 25 , breast cancer 8 , acute myelogenous leukemia 26 , oral squamous cell carcinoma and thyroid cancer 27 . Recent studies have confirmed that CTSB is rarely expressed in normal brain tissues but overexpressed in glioblastoma (GBM) and glioblastoma stem cells (GSCs) 28 , 29 .…”

Insights Into Vascular Anomalies, Cancer, and Fibroproliferative Conditions: The Role of Stem Cells and the Renin-Angiotensin System

“…The RAS may affect the expression of stemess-associated markers in cancer ( 186 ) and CSCs either directly or indirectly via its influence on the TME directly and by its interaction with the immune system ( 5 , 35 ). Targeting the RAS, its bypass loops and converging signaling pathways to achieve optimal blockade of the RAS to regulate CSCs has been proposed ( 3 – 5 ).…”