Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFβ signaling

ABSTRACT

Objective:

Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear.

Methods:

Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFβ expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial–mesenchymal transition (EMT) in vivo.

Results:

OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFβ signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression.

Conclusions:

IH promotes lung cancer progression by upregulating TGFβ signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

KEYWORDS:

• OSA
• intermittent hypoxia
• TGFβ
• CAFs
• lung cancer
• inflammation
• cancer progression
• migration

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Project of the Shanghai Municipal Health Commission [grant number 202040158].