Opinion Review
Copyright ©The Author(s) 2021.
World J Gastrointest Oncol. Feb 15, 2021; 13(2): 92-108
Published online Feb 15, 2021. doi: 10.4251/wjgo.v13.i2.92
Table 1 Tumor initiating cell origination from cell-cell fusion
Cell I
Cell II
Cell fusion method
Cell fusion evidence
Tumor initiating method
Tumor initiating evidence
Mechanism
Ref.
Colorectal cancer cellHuman dendritic cellIn vitro. DCs and cancer cells fused using PEGPurified cellsEnhanced induction of antigen-specific CTLStreptococcal preparation OK-432 promotes fusion efficiency[69]
Human esophageal carcinomas cellHuman dendritic cellIn vitro. ECs and DCs fused using PEGCo-expression of MHC class II, CD86, and MUC1Induced specific antitumor response[55]
Human gastrointestinal cancer cellHuman dendritic cellIn vitro. Fusion via PEG and electroporationTh1/Th2 and Tc1/Tc2 balance improved[73]
Human gastric cancer cellHuman dendritic cellFACS analysisInduced CTLs, reduced metastases[56]
Human gastric cancer cell (HGC-27 or SGC-7901)hucMSCIn vitro. GC-DIO and hucMSCs-DID fusion using PEGDouble positive cellsBALB/C nude mice (2 × 106 cells)In vivo. Tumors formed from fused cells [44]
Human breast cancer cell (MDA-MB-231)Human MSCIn vivo. 2 × 106 MSC300415-GFP and 2 × 106 MDA-MB-231-cherry subcutaneously injected into 5 female NOD/SCID miceHybrid cells GFP/cherry fluorescence1 × 106 MDA-hyb3-GFP/cherry cells were injected subcutaneously into 3 female NOD/SCID miceIn vivo. Tumors formed from fused cells [80]
Human colon adenocarcinoma cellHuman HeLa cell (D98OR)In vitro. Fused using PEG, isolation of hybrid cells by selecting isolated coloniesFlow cytometry analysis had more DNA than expected. A range of 71–140 chromosomesFusion cell characteristics were consistent with cancer cells[75]
Human colon cancer cell (SW480)Human dendritic cellIn vitro. Tumor cells- PKH26-red and DCs- PKH67-green fused using PEGDual red and green fluorescence and highly expressed CD80, CD86, and HLA-DRCD8+ T lymphocytes co-cultured with dendritic cells at a ratio of 10:1CTLs were activated to proliferate and the number of T cells increased[55]
Human colon cancer cell (SW620)Human dendritic cellIn vivo. DCs and tumor cells fused using PEGFusion efficacy was evaluated by FM and FCIn vivo. 1 × 107 fusion hybrids injected intraperitoneallyCellular immune responses, significant inhibition of tumor growth[55]
Human colon carcinoma line (VACO-411)Human breast cancer line (MCF-7)In vitro. VACO-411 (1 × 106 cells) and MCF-7 (1 × 106 cells) fused using PEGMorphology of VACO-411 × MCF-7 fused cellsIn vitro. The fused cells were treated with TGF-βFusion cells were inhibited by TGF-β[76]
Human colon epithelial cancer cellHuman normal colon cellIn vitro. Cancer cells and normal cells (1:10) fused using PEG Comparison of DNA synthesis (P < 0.01)Male mice nu/nu injected subcutaneously with1 × 106 fused cellsThe fused cells could not grow into tumors[77]
Human colorectal carcinoma cellHuman dendriticcellIn vitro. DCs-CMFDA-green,colorectal carcinoma-CMTMR-red cells fused using PEG/electrofusionDouble-positivecellsEfficiently activated autologous tumor-specific T cells[68]
Human esophageal cancer cell (EC109)Human dendritic cellIn vitro. DCs and ECs (5:1-10:1) fused using PEGCo-expression of MHC-CiaSSII and CD86 and MUC1 antigensCytotoxic T lymphocytesAntitumor capabilities[60]
Human esophageal cancer cell (EC9706)hucMSCIn vitro. ECs-DiO hMSCs- DiD fused using PEG Double positive hybrids are yellow and multinuclearIn vivo. Xenograft assays in immunodeficient miceBoth ECs and their self-fusion groups developed tumors
Human esophageal carcinoma cell (EC9706)Human hemopoietic stem cell In vitro. ECs and HSCs (10:1) fused using PEGCD34+CD38-Scal+ cells isolated using immunomagnetic beads; HSCs cannot grow in DMEM supplemented with 10% FBSIn vivo. 5 × 105 fused cells injected into 12 NOD/SCID miceAll mice formed tumors; however, the tumor weight of the fused cell group was lower than that of the EC9706 group[54]
Human esophageal carcinoma cellHuman dendritic cellIn vitro. DCs and ECs (5:1) fused using PEG; incubated with FA-FITC and CD80-PEAnalysis using FATICanIn vivo. Fusion vaccine (0.2 mL; 1 × 106 cells) injectedAnti-tumor effects [58]
Human esophageal carcinoma cell (EC109)Human dendritic cellIn vitro. DCs and ECs (5:1) fused using PEG. FA-FITC CD80-PE mAbs-CD80, CD83 and CD86FCIn vitro. Cytotoxicity assays Antitumor activity[59]
Human female pancreatic adenoepithelial neoplasm cell Human male BMDC In vivo. 4 female pancreatic cancer patients transplanted with male BMDCs Peripheral blood cell: EpCAM (yellow)/CD45 (green), Y chromosome, CK+/CD45+, MФ proteinsCD14, CD16, CD11c, CD163 MUC4[43]
Mouse colon cancer cell (MC38)Mouse R26R- YFP Cre miceIn vivo. MC38 cells were injected ventrally into r26R-YFP Cre miceRFP+ YFP+[51]
Mouse primary melanoma cellMouse MФMelanoma cells were injected into mice intradermallyRFP and GFP cells300 and 3000 cells, respectively injected into mice (n = 9, 3)Tumor initiationThe characteristics of parental cells provided adhesive affinity[51]
Human gastric cancer cell (MKN-1)Dendritic cellIn vitro. DCs- PKH-26 and GC cells-PKH-67 fused via PEG/electrofusion Double positive cell populationsIn vitro. Co-cultured DCs (1 × 105 cells) with 1 × 106 T cellsInduced tumor antigen-specific CD8+ T cells[70]
Human gastric epithelial cell (GES-1)CM-MSCIn vitro. GES-1- PHK-26 (2 × 106 cells) and CM-MSCs- CFSE (1 × 107) cells fused using PEGMost cells express PKH26 and CFSEIn vivo. The fused cells (1 × 107cells) were injected into 8 BALB/c nude miceTumors from the fused cells formed in vivo[47]
Human gastric cancer cell (SGC7901)Human dendritic cellIn vitro. SGC7901 and DCs fused using PEG Pure fused cells were obtained by selective culture with HAT/HT culture systemIn vivo. Fusion cells (5 × 108) were injected into BALB/c miceIn vivo. The fused cells could not grow into tumors[61]
Human gastric cancer cell (SGC7901)Human dendritic cellIn vitro. SGC7901 and DCs fused using PEG Selective culture with the HAT/HT culture systemIn vivo. Fused cells (5 × 106/mL) + T cells (5 × 106/mL)In vivo. The fused cells could not grow into tumors[62]
Human hepatobiliary stem/progenitor cellHuman hematopoietic precursor-derived myeloid intermediateIn vitro. Cultures of CD34+ LTICs and xenograft cells (the xenografts were produced by CD34+ hybrid cells)CD34+ LTICs co-expressed liver stem cell and myelomonocytic cell markersHSPCs were fused with a CD34+ hematopoietic precursor-derived myeloid intermediate to form CD34+ hybrid cells
Human hepatocellular carcinoma cell (HepG2)Human embryonic stem cell In vitro. HepG2-red mitochondrion selective probe and hESCs-Oct-GFP cells fused via laser-induced single-cell fusion Transfer of cytoplasmic GFP from hESCs to HepG2 cellsIn vivo. HepG2 cells and the fused cells (5 × 104 and 1 × 105 cells, respectively) were injected into nude miceTumors were generated from fused cells
Human hepatocellular carcinoma cell (HepG2)Mouse MSC In vitro. MSCs- DiI (5 × 105 cells) and HepG2-eGFP (1 × 105 cells) fused using PEGDual fluorescence, two nucleiIn vivo. The fused cells were injected into 7 nude mice/group with 2.4 × 107 cells/groupTumors were formed from fused cells
Human intestinal cancer cell (HT-29)Human MSCIn vitro. PM7-eGFP and HT-29-DsRED cells were coculturedeGFP and DsRED double positive cellsAcquired epithelial characteristics[51]
Human intestinal epithelial cells Human hematopoietic cellIn vitro. X- and Y-chromosome determined by FISH. Female recipients of hematopoietic cell transplant from male donorsStained for X- (green) and Y- (red) chromosomes and Lamin B1 (white)In mice, hematopoietic fusion with non-hematopoietic cell types occurs endogenously in the absence of disease[86]
Mouse intestinal epithelial cellMouse bone marrow-derived cellIn vivo. CMV-CreGFP+ mice BM were transplanted into iDTR miceCo-staining for GFP and EpCAM.GFP+ cells in the intestineCell fusion is dispensable for tissue homeostasis[52]
Mouse intestinal stem cellHuman bone marrow-derived cellIn vivo. Donor female mice BMDCs-GFP, male recipient miceEGFP expression in all principal intestinal epithelial lineages[63]
Mouse colon adenocarcinoma cell (CT26)Mouse dendritic cellIn vitro. Tumor cells- PKH67-Green and DCs fused using PEG Assessedvia the trypan-blue exclusion testIn vivo. BALB/c mice injected with 5 × 105 cells The fused cells could not generate tumors[64]
Mouse colon adenocarcinoma cell line (CT26)Mouse dendritic cellIn vitro. DCs-anti-CD11cmAb and tumor cells- CFSE fused using PEG Analyzed by FCIn vivo. Injection of 1 × 104, 105, or 106 cells/mouseThe fused cells did not generate tumors. CTL anti-tumor effects[72]
Mouse colon carcinoma cells (CT26CL25)Allogeneic and semi allogeneic dendritic cellsIn vitro. DCs-PKH26-red andCT26CL25-PKH67-green fused using PEG Analyzedby FCIn vivo. 1 × 106 fused cells and 5.0 × 105 CT26CL25 cellsAnti-tumor effects in vivo[65]
Mouse colon epithelial cellMouse BMDCIn vivo. Female mice BMDCs-GFP (1 × 107 cells) transplanted into irradiated male mice Co-expression of GFP and the Y chromosomeIn vivo. Parabiosis surgery (GFP and ROSA mice)Bone-marrow/epithelial cell fusion causes genetic reprogrammingInflammation and proliferation act together to mediate intestinal cell fusion[87]
Mouse gastric epithelial cellMouse BMDCIn vivo. Male irradiated C57BL/6 mice received female C57BL/6 mice BMDC-GFP Direct. Positive for the Y chromosome and expressed GFP as determined by FMIn vivo. GCs were induced with a carcinogen Tumor formed from fused cells in vivoChronic inflammation (adenocarcinoma, glandular stomach, not squamous cell carcinoma)[48]
Mouse hepatocellular carcinoma cellMouse dendritic cellIn vitro. HCCs PKH-26-red and DCs-PKH-2-green fused using PEGThe fusion cells were yellow under the confocal microscopeIn vitro. CTL assayIn vitro. Activated cytotoxic T lymphocytes[66]
Mouse hepatoma cell line (Hepa1-6)Mouse embryonic stem cellIn vitro. Cancer cells-GFP and ES cells-RFP fused using PEGDouble fluorescence-positiveIn vivo. 1 × 106 ES-cancer fused cells injected into nude miceTumor formed from fused cells in vivo
Mouse intestinal epithelial cancer cellMouse WBM (macrophage)In vivo. WBM-GFP (5 × 106 cells) injected in recipient mice (male WT, ApcMin/+, ROSA26, ROSA26/ApcMin/+). ParabiosisCo-localization of GFP (green) and β-galactosidase (red)Nuclear reprogrammingFusion between circulating blood-derived cells and tumor epithelium origin at the natural course of tumorigenesis[39]
Mouse intestinal epithelial cells (IEC-6). Human cervical adenocarcinoma cells (HeLa)Mouse intestinal epithelial cells (IEC-6) Human cervical adenocarcinoma cells (HeLa)In vitro. IEC-6- CFSE andIEC-6- SNARF-1 (HeLa -Cy3-dUTP-red and HeLa- Cy5-dUTP-green) fused using PEGThe fused cell emits both CFSE and SNARF-1 fluorescence (IEC-6). Eight daughter cells contain both dyes (HeLa)In vivo. The IEC-6 fused cells (Two million cells) were injected in 18 miceTumor formed from the fused cells in vivo (n = 11 generated tumors)[78]
Mouse intestine stromal cellMouse bone marrow-derived macrophageIn vivo. Female mice BMDCs-GFP injected in male recipient miceCo-localization of GFP and Y-chromosomeOrgan fibrosisDepleting macrophages genetically reduced the number of cells[53]
Mouse prostate cancer cell (PCa)Mouse BMDCIn vivo. 2 × 106 cells/mice BMDCs-GFP transplanted into 10 C57BL/6 miceCo-expression of GFP and CK8C57BL/6 mice-GFP, induced prostate cancer by MNUGFP-positive cells in the prostate cancer tissue[79]
Whole tumor cellHuman dendritic cellIn vitro. The purified DCs and tumor cells fused using PEG[67]