Table 1 Tumorigenic effects exerted by prematurely senescent (RT-induced) normal fibroblasts
From: Cancer-associated fibroblasts in radiotherapy: Bystanders or protagonists?
Ref. | Fibroblast type | Tumor model | Experimental model | Effects |
|---|---|---|---|---|
Rodier [82] | HCA2 NF cell line | None | In vitro (co-cultures) | Enhanced expression of IL-6 and IL-8 by IR-induced senescent fibroblasts |
Ohuchida [85] | MRC5 cell line CAFs/1 donor | Pancreas | In vitro (co-cultures) | Irradiated NFs increase invasiveness of cancer cells. Increased phoshorylation of HGF receptor in tumor cells |
Papadopoulou [30] | Normal human lung FBs | Lung | In vitro In vivo (subcutaneous) | Enhanced tumor growth after co-injections with IR-induced senescent fibroblasts |
Kamochi [81] | NF cell lines (WI-26 VA4, NIH 3T3) | Oral SSC | In vitro | Irradiated NFs promote invasive growth of OSCC cells |
Patel [79] | NFs cell lines | Esophageal cancer | In vitro | Conditioned medium from irradiated FBs promotes enhanced migration & invasion of normal epithelial cells |
Tsai [80] | Primary human NF | Breast cancer | In vitro (3D-cultures) | Enhanced expression of MMPs by senescent NFs. Increased ECM catabolism |
Tsai [86] | Primary human NF | Breast cancer | In vitro (co-cultures) | Increased tumor cell radio-resistance by senescent NFs |
Tachiiri [27] | NFs | None | In vitro | Gene expression profiles after γ-IR |
Arshad [87] | Murine lung NFs | Lung cancer | In vitro (supernatants) | Fibroblasts do NOT modulate tumor cell radio-resistance. Reduced TGF-β and MMP release after IR |
Steer [88] | NF cell lines NIH-3T3, L929 | None | In vitro (3D co-cultures), In vivo (co-inject) | Different outcomes with different tumor cell/fibroblasts combinations |
Barcellos-Hoff [84] | Mammary gland tissue | Breast cancer | In vivo (Mammary gland irradiation) | Increased tumor growth of malignant and premalignant tumor cells in pre-irradiated mammary glands |
Liu [76] | Human NFs | Suprarenal capsule | In vivo (co-injections) | Premature senescent NFs do NOT confer growth-stimulatory effects |
Al-Assar [83] | PSC (non-tumoral) | Pancreatic cancer | In vitro (3D) In vivo (co-injections) | PSC enhance EMT and CSC processes via TGF-β-dependent mechanisms |