Table 1 Main findings of the cross talk between CAFs and cancer cells during radiotherapy

Tommelein et al.,2017

[22]

CRC

1. RT cause DNA damage, p53 activation, cell-cycle arrest and IGF-1 secretion in CAFs

2. RT-activated CAF promoted CRC cells survival and metabolic switch

3. RT followed by IGF-1R neutralization reduced organ metastases in orthotropic model

4. mTOR was significantly higher in Rectal Cancer patients after neoadjuvant CRT

Zhang et al., 2017

[37]

ESCC and adjacent normal tissue

1. CAFs induced radioresistance by secreting CXCL1

2. CXCL1 expression was an independent prognostic factor for patients receiving CRT

Grinde et al., 2017

[26]

NSCLC

1. CAFs viability, adhesion did not affected by single-high dose radiation and fractionated doses radiation.

2. Radiation abolished CAFs protumorigenic capacity in the coinjection model in mice.

Wang et al., 2017

[38]

Foreskin, lung cancer

CAF promoted tumor cells DNA damage repair after radiation via mTOR-mediated autophagy

Li et al., 2016

[31]

Pancreatic cancer and adjacent normal tissue

1. Radiation enhanced CAFs migration- and invasion-promoting capacity

2. CXCL12 secreted by CAFs was increased after radiation, which enhanced tumor invasion and EMT

Verset et al., 2015

[34]

Rectal cancer

1. Patients underwent neoadjuvant CRT showed higher a-SMA/neoplastic epithelial area ratio

2. The alpha-SMA/epithelial area ratio above 1 is associated with poor recurrence-free survival

(Matsuoka et al., 2015

[33]

OSCC

High level of CAFs were correlated with advanced pT- and pN- stage and poor prognosis

Ji et al., 2015

[51]

NSCLC

1.CAFs promoted cocultured lung cancer cells radioresistance in vitro

Bao et al., 2015

[32]

ESCC and adjacent normal tissue

2.Irradiated fibroblasts increased ESCC cells invasiveness with decreased E-cadherin and increased vimentin expression

Arshad et al. 2015

[28]

primary murine lung fibroblasts

CM from irradiated fibroblasts did not change TC-1 cell radiation sensitivity but stimulated their migration and increased their Vimentin and Snail expression

Chu et al. 2014

[36]

CESE

1.CM from CAFs increased irradiated Hela cell survival

2.Such effect was enhanced by using CM from mixed culture of CAFs and HeLa cells

Boelens et al., 2014

[41]

MRC-5 fibroblasts

1.Exosomes transferred from MRC-5 fibroblasts induced the interferon-related DNA damage resistance signature (IRDS) in breast cancer cells

2. In xenograft mouse model, coinjected MRC-5 fibroblasts protected breast cancer cells from 8 Gy RT and maintained tumor growth compared to single breast cancer cell group.

Hellevik et al., 2013

[25]

NSCLC

1. Ablative ionizing radiation (AIR) on CAFs result in

1) downregulated secretion of angiogenic factors such as SDF-1, angiopoietin, and TSP-2

2) upregulated secretion of bFGF;

3) unaffected expression levels of HGF, IL-1β, IL-6, IL-8 and TNF-α

2.Irradiated CAFs did not affect H-520/H-522 proliferation or migration

3. CM from irradiated CAFs reduced HUVECs cells migration

Hellevik et al., 2012

[23]

NSCLC

1. AIR induced cellular senescence and inhibited proliferation, migration and invasion in CAFs.

2.AIR promoted MMP-3 and inhibited MMP-1 expression in CAFs

3. AIR enhanced CAFs surface expression of integrin 2, 1 and 5

Saigusa et al., 2011

[35]

Rectal cancer

1. In rectal cancer, FAP-α and SDF-1 were mainly expressed in CAFs

2. Positive expression of FAP-α and SDF-1 predicted distant recurrence

Kamochi et al., 2008

[29]

Wi26 VA4 fibroblast (SV40-transformed

1. Radiation reduced both the number of NIH 3 T3 and WI-26 VA4 fibroblasts after 15 days.

human lung fibroblasts); NIH 3T3 fibroblast

2. Irradiated fibroblasts enhanced the invasion of SCC cells and had no impact on their apoptosis

3. Irradiated fibroblasts expressed high TGF-1 compared to control

Weichselbaum et al., 2008

[40]

MRC-5 fibroblast

Exosomes transferred from MRC-5 fibroblast activated IRDS and anti-viral/NOTCH3 pathway in breast cancer cells to enhance their radioresistance in vitro and in mice models

Ohuchida et al., 2004

[30]

human fibroblast cell line MRC5, primary pancreatic fibroblasts

1. 5-Gy/10-Gy irradiation on fibroblasts partially inhibited proliferation but caused no cytolytic after 24 h

2. Irradiated fibroblasts enhanced pancreatic cancer cells invasiveness in a radiation dose(0, 5 10 Gy) dependent manner

3. Irradiated fibroblasts increased both phosphorylation and expression of c-Met as well as the MAPK activity of pancreatic cancer cells