Crosstalk with cancer-associated fibroblasts increases the growth and radiation survival of cervical cancer cells.
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.
a  Institute of Medical Science, Tzu Chi University, Taiwan, R.O.C.;
Tang-Yuan
TY
Chu
June-Ting
JT
Yang
Tien-Hung
TH
Huang
Hwan-Wun
HW
Liu
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002450:Cell Communication; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000528:radiation effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects / Q000637:transplantation; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000528:radiation effects; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D017077:Culture Media, Conditioned; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C070114:BTG2 protein, human