Table1 Studies focus on how tobacco altered fibroblasts affect the microenvironment and epithelial cells in proximity
Author | Year | Type of epithelia cells | Type of fibroblast | Treatment | Main result |
|---|---|---|---|---|---|
In Vitro experiment | |||||
Marina [7] | 2019 | human head and neck carcinoma cells (CAL27,FaDu) | Mouse Embryonic Fibroblasts Normal human fibroblasts from skin | CSE | 1. CSE induces senescence and glycolysis in fibroblasts and CSE exposed fibroblasts can promote mitochondrion OXPHOS in head and neck carcinoma cells 2. Co-culture with CSE-fibroblasts increases features of tumor aggressiveness and proliferation 3. MCT4 expression in tumor stroma is associated with the prognosis of head and neck cancer |
Chen [11] | 2017 | human and breast cancer cell lines (MCF-7, MDA-MB-231) | human embryonic lung fibroblast cells (WI38) | nicotine | 1. Nicotine induces myofibroblastic differentiation and Nicotine-treated fibroblasts promote the EMT of breast cancer cells 2. Secretion of CTGF and TGF-β from nicotine-treated fibroblasts enhances breast cancer migration 3. Nicotine induces expressions of CTGF and TGF-β through an α7 nAChR-dependent AKT/TAZ signaling mechanism |
Daniel [69] | 2016 | Human paracrine cancer cell lines (PANC-1, Mia-PaCa-2, BxPC3) | tumor associated fibroblast of pancreatic cancer | nicotine | 1. Nicotine treatment augments HGF-MET-mediated paracrine signaling between tumor associated fibroblasts and pancreatic cancer cells, thus promoting tumor growth and metastasis 2 The expression of phosphorylated c-Met directly correlates with reduced overall survival in pancreatic cancer |
Melling [43] | 2013 | oral squqmous carcinoma cell line (SCC4, H357) | primary normal oral fibroblasts | CSC | 1. CSC induces changes in miRNA expression in oral fibroblasts and. miR-145 re-expression reverses CSC-induced OSCC chemotaxis |
Salem [36] | 2013 | human triple-negative breast cancer (MDA-MB-231) | Human immortalized fbroblasts (hTERT-BJ1) | CSE | 1. CSE induces senescence and DNA damage in stromal fbroblasts by activating the p53-p21-pRb pathway 2. CSE treatment promotes autophagy and mitophagy, downregulating the expression of mitochondrial OXPHOS complexes in fibroblasts 3. CSE-treated fbroblasts produce high levels L-lactate and ketone bodies, indicative of mitochondrial dysfunction: A shift toward glycolysis and ketogenesis |
Coppe [68] | 2008 | two nonmalignant keratinocyte cell lines (DOK,HaCAT) normal human epidermal keratinocytes (NHEK; Cambrex) oral squamous cell carcinoma cell lines (HSC-3) | Normal human fibroblasts from skin Normal human fibroblasts from oral mucosa Normal human fibroblasts from embryonic lung | STE | 1. STE promote proliferation of fibroblasts and Induce ROS production and oxidative DNA damage in fibroblasts 2. STE alter the secretory phenotype of fibroblasts thus stimulating proliferation of skin and oral keratinocytes 3. STE–exposed fibroblasts stimulate Interstitial Invasion of oral epithelial cells and down-regulate cell polarization and keratinization markers |
Hou [37] | 2020 | Nonsmall lung cancer cell line (CL1-0) | human lung fibroblast cell line (MRC-5) | CSE | 1. CSE-treatment promotes autophagy in fibroblasts 2. CSE-treatment fibroblasts promote the invasion of cancer cells in 2D and 3D model with secretion of IL-8 |
In Vivo experiment | |||||
Marina [7] | 2019 | human head and neck carcinoma cells (CAL27,FaDu) | Athymic nude mice | CSE | 1. Co-injection of carcinoma cells with CSE-fibroblasts increases tumor growth |
Salem [36] | 2013 | human triple-negative breast cancer (MDA-MB-231) | Athymic nude mice | CSE | 1. CSE-treated fbroblasts enhance tumor growth, independently of neo-angiogenesis |
Daniel [69] | 2016 | surgically resected primary pancreatic adenocarcinoma | Athymic nude mice | nicotine | 1. Physiologic doses of nicotine significantly promote the growth and metastasis of tumor 2. Physiologic doses of nicotine induced activation of c-Met within the tumor microenvironment |