Journal Article

Crosstalk with Cancer-Associated Fibroblasts Increases the Growth and Radiation Survival of Cervical Cancer Cells

Liu, Hwan-Wun, Yang, June-Ting, Chu, Tang-Yuan, Huang, Tien-Hung

2014

Overview

Crosstalk between cancer cells and the surrounding cancer associated fibroblasts (CAFs) plays an illusive role in cancer radiotherapy. This study investigated the effect of cancer cell–cancer associated fibroblasts crosstalk on the proliferation and survival of irradiated cervical cancer cells. A pretreatment with conditioned medium from a mixed culture of CAF and HeLa cells (mixCAF) had a stronger effect on enhancing the proliferation and survival of irradiated HeLa cells compared to pretreatment with CAF conditioned medium alone. In addition, pretreatment with a mixed culture of CAF and HeLa cells conditioned medium reduced the levels of two major radiation-induced genes, GADD45 and BTG2, and phosphorylation of p38. Profiling of the growth and survival factors in the conditioned medium revealed PDGF and VEGF, and IGF2, EGF, FGF-4, IGFBPs and GM-CSF to be specifically secreted from HeLa cells and CAFs, respectively. This study demonstrated radiation protective effects of CAF-cancer cell crosstalk, and identified multiple growth factors and radiation response genes that might be involved in these effects.

• Publisher: The Radiation Research Society,Radiation Research Society,Allen Press Inc
• Subject: Animals / Cancer / Carcinoma, Squamous Cell - pathology / Cell Communication / Cell Cycle Proteins - biosynthesis / Cell Cycle Proteins - genetics / Cell Division - radiation effects / Cell growth / Cervical cancer / Coculture Techniques / Conditioning / Crosstalk / Culture / Culture Media, Conditioned - pharmacology / Cultured cells / Epithelial Cells - pathology / Epithelial Cells - radiation effects / Epithelial Cells - secretion / Female / Fibroblasts / Fibroblasts - pathology / Fibroblasts - secretion / Gene expression / Gene Expression Regulation, Neoplastic - radiation effects / Genes / Growth factors / HeLa cells / HeLa Cells - radiation effects / HeLa Cells - secretion / HeLa Cells - transplantation / Humans / Immediate-Early Proteins - biosynthesis / Immediate-Early Proteins - genetics / Intercellular Signaling Peptides and Proteins - secretion / Mice / Mice, Inbred NOD / Mice, SCID / Neoplasm Proteins - biosynthesis / Neoplasm Proteins - genetics / Neoplasm Proteins - secretion / Neoplasm Transplantation / Nuclear Proteins - biosynthesis / Nuclear Proteins - genetics / p38 Mitogen-Activated Protein Kinases - metabolism / Phosphorylation - radiation effects / Pretreatment / Protein Processing, Post-Translational - radiation effects / Radiation Tolerance / Radiotherapy / Real-Time Polymerase Chain Reaction / REGULAR ARTICLE / REGULAR ARTICLES / Stromal Cells - pathology / Stromal Cells - secretion / Survival / Tumor Microenvironment / Tumor Stem Cell Assay / Tumor Suppressor Proteins - biosynthesis / Tumor Suppressor Proteins - genetics / Uterine Cervical Neoplasms - pathology