Neutrophil extracellular traps in gastrointestinal cancer

Table 1 Role of neutrophil extracellular traps in gastric cancer

Ref.	Cell lines	Model (in vitro, in vivo, human)	Conclusion
Yang et al[64], 2015	-	Human	NETs contribute to the hypercoagulable state in GC patients with stage III/IV
Kanamaru et al[68], 2018	MKN45, NUGC-4, OCUM-1	In vitro, in vivo	NETs on peritoneal surface assist the clustering and growth of GC tumor cells disseminated in abdomen
Tao et al[74], 2018	BGC-823	In vitro, in vivo	NET formation is inhibited by Sal B and DHT I at the earlier stage
Kumagai et al[72], 2020	MKN45, NUGC-4, OCUM-1	In vitro, human	NETs formation is enhanced under surgical stress and can effectively trap circulating tumor cells
Li et al[78], 2020	BGC-823, SGC7901, MKN28	In vitro, human	NETs destruction promotes the apoptosis and inhibits the invasion of gastric cancer cells by regulating the expression of Bcl-2, Bax and NF-κB
Zhang et al[94], 2020	-	Human	NETs have novel diagnostic, therapeutic predictive, and prognostic value in GC patients

NETs: Neutrophil extracellular traps; GC: Gastric cancer.

Table 2 Role of neutrophil extracellular traps in colorectal cancer

Ref.	Cell lines	Model (in vitro, in vivo, human)	Conclusion
Arelaki et al[81], 2016	Caco-2	In vitro, human	NETs concentration is gradually reduced from the tumor mass to the distal margin
Tohme et al[83], 2016	MC38	In vitro, human	Surgical stress and intratumoral hypoxia induce NETs formation and NETs can trigger HMGB1 release and activate TLR9-dependent pathways to promote adhesion, proliferation, migration, and invasion in CRC
Richardson et al[84], 2017	-	Human	NET production in the later postoperative period appears to coincide with surgical recovery
Arelaki et al[88], 2018		Human	PolyP is present in human colon cancer and increase NETosis
Rayes et al[82], 2019	MC38, H59	In vitro, in vivo, human	Circulating NET levels are elevated in advanced CRC and blocking NETosis significantly inhibits spontaneous metastasis to the lung and liver
Yazdani et al[89], 2019	MC38, HCT116, Hepa 1-6, Huh7	In vitro, in vivo, human	NETs facilitate the growth of stressed cancer cells by altering their bioenergetics
Zhang et al[80], 2019	HUVECs	In vitro, human	NETs are involved in the progression of CRC and act as potential agonists in CRC-related hypercoagulability
Rayes et al[113], 2020	HT-29, MC38, A549	In vitro, in vivo, human	NET-associated CEACAM1 acts as a putative therapeutic target to prevent the metastatic progression of colon carcinoma
Shang et al[92], 2020	DKs-8, DKO-1, PMN	In vitro, in vivo, human	Exosomes may transfer mutant KRAS to recipient cells and trigger increases in IL-8 production, neutrophil recruitment and formation of NETs, eventually leading to the deterioration of CRC
Xia et al[105], 2020	MC38, HepG2	In vitro, in vivo	AAV-mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC
Yang et al[91], 2020	HT29, MC38	In vitro, in vivo, human	A novel positive feedback between elevated tumorous IL-8 and NETs can promote CRC liver metastasis
Yang et al[93], 2020	HCT116, MDA-MB-231, MCF-7, 4T1, HEK293T, HeLa, E0771	In vitro, in vivo, human	CCDC25 mediates NET-dependent metastasis and is suggested to be a therapeutic target for the prevention of cancer metastasis

NETs: Neutrophil extracellular traps; CRC: Colorectal cancer; AAV: Adeno-associated virus.