Tissue-specific Physical and Biological Microenvironments Modulate the Behavior of Cervical Squamous Cell Carcinoma

The mechanisms controlling the aggressiveness and survival of cervical SCC cells remain unclear. We investigated how the physical and biological microenvironments regulate the growth, apoptosis and invasiveness of cervical cancer cells. Dynamic flow and air exposure were evaluated as physical microenvironmental factors, and stromal fibroblasts were evaluated as a biological microenvironmental factor. To investigate any regulatory effects of these microenvironmental factors, we established a new culture model which concurrently replicates fluid streaming, air exposure and cancer-stromal interactions. Three cervical cancer cell lines were cultured with or without NIH 3T3 fibroblasts. Air exposure was realized using a double-dish culture system. Dynamic flow was created using a rotary shaker. Dynamic flow and air exposure promoted the proliferative activity and decreased the apoptosis of cervical cancer cells. Fibroblasts regulated the invasive ability, growth and apoptosis of cervical cancer cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by dynamic flow, air exposure and cellular interactions, depending on the cervical cancer cell type. This study demonstrates that the physical and biological microenvironments interact to regulate the aggressiveness and survival of cervical cancer cells. Our simple culture system is a promising model for developing further treatment strategies for various types of cancer.

Automated summary

The study investigates the regulatory effects of the physical and biological microenvironments on the aggressiveness and survival of cervical SCC cells. Results show that dynamic flow, air exposure, and stromal fibroblasts influence the growth, apoptosis, and invasiveness of cervical cancer cells, and modulate the extracellular signal-regulated kinase and p38 signaling pathways in a cell-type dependent manner.