Growth Hormone Action as a Target in Cancer: Significance, Mechanisms and Possible Therapies

Endocrine Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Growth hormone (GH) is a pituitary derived endocrine required for normal post-natal growth and development. Hypo or hypersecretion of GH results in two pathologic conditions, namely deficiency (GHD) acromegaly. Additionally, also produced non-pituitary tumoral tissues where it acts rather as cellular factor with an autocrine/paracrine mode action. An increasingly persuasive large body evidence over the last 70 years concur that action implicit escalating several cancer-associated events, locally systemically. This pleiotropy GH's effects puzzling, but association cancer-risk automatically raises concern patients acromegaly individuals treated GH. By careful assessment available knowledge on fundamental concepts cancer, suggestions from epidemiological clinical studies, specific reports, this review we aimed to help clarify distinction vs. promoting cancer reconcile discrepancies between experimental data. Along discourse, critically weigh targetability - firstly by detailing molecular mechanisms which posit critical node tumor circuitry, secondly, enumerating currently therapeutic options targeting On basis our discussion, infer targeted intervention appropriate patient population can benefit sizeable subset current prognoses.

Language: Английский

Unveiling immune cell response disparities in human primary cancer-associated fibroblasts between two- and three-dimensional cultures

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0314227 - e0314227

Published: Dec. 19, 2024

Cancer-associated fibroblasts (CAFs) play pivotal roles in solid tumor initiation, growth, and immune evasion. However, the optimal biomimetic modeling conditions remain elusive. In this study, we investigated effects of 2D 3D culturing on human primary CAFs integrated into a modular microenvironment (TME). Using single-nucleus RNA sequencing (snRNAseq) Proteomics’ Proximity Extension Assays, characterized CAF transcriptomic profiles cytokine levels. Remarkably, when cultured 2D, exhibited myofibroblast (myCAF) subtype, whereas spheroid cultures, displayed more inflammatory (iCAF) pathological state. By integrating single-cell gene expression data with functional interrogations critical TME-related processes [natural killer (NK)-mediated killing, monocyte migration, macrophage differentiation], were able to reconcile form function. TME models, enhance cancer cell growth immunologically shield cells from NK cell-mediated cytotoxicity, striking contrast their counterparts. Notably, CAF-secreted proteins manifest immunosuppressive profile by enhancing transendothelial migration differentiation M2-like tumor-associated macrophages (TAMs). Our findings reveal clinically relevant desmoplastic model that can be employed industrial drug discovery campaigns expand cellular target range chemotherapeutics.

Language: Английский