Cigarette smoking is a well-known risk factor in the development and progression of malignant diseases.
Nicotine, the major constituent in cigarette
smoke, has also shown negative effects on stem cells. Mesenchymal stem cells (MSCs) have been widely demonstrated to migrate into
tumors and play key roles in
cancer progression. However, the mechanisms by which
nicotine impacts MSCs and
tumorigenesis of
lung cancer are still undetermined. In this study we investigated the effects of
nicotine on human umbilical cord mesenchymal stem cells (hUC-MSCs) and the impacts of
nicotine-treated hUC-MSCs on
tumor formation and progression. We found that
nicotine has a toxic effect on hUC-MSCs and changes the morphology, inhibits proliferation and promotes apoptosis of hUC-MSCs in a dose-dependent manner.
Nicotine-treated hUC-MSCs produce higher level of
IL-6. Moreover,
nicotine promotes migration, stemness and epithelial-mesenchymal transition (EMT) of hUC-MSCs by inhibiting
E-cadherin expression and upregulating mesenchymal markers such as
N-cadherin and
Vimentin, leading to the induction of stem cell markers Sox2, Nanog, Sall4, Oct4 and CD44. Migration and proliferation of
non-small cell lung cancer A549 cells and
breast cancer MCF-7 cells are promoted after their coculture with
nicotine-treated hUC-MSCs in a cell-cell contact-independent manner. Furthermore,
nicotine-treated hUC-MSCs promote
tumor formation and growth of A549 cells in nude mice. These studies demonstrated that the enhanced stemness and EMT of hUC-MSCs induced by
nicotine are critical for the development of tobacco-related
cancers.