Table 3.
Implication of NG2/CSPG4 in tumour progression as suggested by in vivo studies1
| Tumour type | Cell line | Host | Targeting agent/ experimental condition |
Effect | Reference |
|---|---|---|---|---|---|
| Xenogenic | |||||
| Triple-negative breast carcinoma | MDA-MB-4352 MDA-MB-231 |
C.B17-SCID | mAb 225.28 | Reduced tumour volume; inhibition of metastasis formation; inhibition of tumour recurrence |
43 |
| Glioblastoma | U87MG | Athymic | mAb 9.2.27-DAVLBHY3 | Reduced tumour volume | 146 |
| Glioblastoma | U87MG Glioblastoma biopsy |
Athymic | mAb 9.2.27-Pseudomonas exotoxin A | Increased survival | 147 |
| Glioblastoma | U87MG U87MG_shRNA4 |
NOD-SCID | TNFα | Diminished drug resistance | 22 |
| Glioblastoma5 | U251 U251-NG2+ |
Athymic | Ionizing radiation | Increased treatment resistance | 70 |
| Glioblastoma/ Melanoma |
U251, U251-NG2 Glioblastoma biopsy A375_shRNA4 |
Athymic (glioblastoma), NOD-SCID (melanoma) |
NG2 shRNA | Reduced tumour volume; impaired angiogenesis | 71 |
| Glioblastoma | U251-NG2+5 Glioblastoma biopsy, U87MG |
Athymic | mAb 9.2.27 + NK cells | Increased survival | 148 |
| Melanoma/ Brest carcinoma/ Head and neck squamous cell carcinoma |
SENMA UACC-812 PCI-30 |
NSG | Redirected T cells with a CSPG4-specific (CAR) with CD28 costimulatory endodomain |
Reduced tumour volume | 145 |
| Melanoma | M21 | Athymic | mAb 9.2.27-Diphtheria toxin A | Reduced tumour volume | 132 |
| Melanoma | Colo38 | Athymic | mAb 225.28S-Purothionin | Reduced tumour volume | 133 |
| Melanoma | M21 | Athymic | mAb 225.28-methotrexate | Reduced tumour volume | 134 |
| Melanoma | FM3, FM55 FMEX, G361, Melanoma biopsy |
NOD-SCID | mAb K305-Staphylococcal enterotoxin A | Redirection of T cells against cancer cells; reduced tumour volume |
135 |
| Melanoma | 518A2 | NOD-SCID | mAb 225.28 | Reduced tumour volume | 136 |
| Melanoma | MM138 | Athymic | mAb 9.2.27-Bi213 | Inhibition of tumor engraftment; delayed tumor growth | 137 |
| Melanoma | 518A2 | C.B.17 SCID/SCID | NG2/CSPG4 mimotope 225D9.2+ | Reduced local growth | 138 |
| Melanoma | MeWo Melanoma biopsy |
NIH-III Mice | Redirected T cells with bispecific anti- NG2/CSPG4-CD20 mAbs |
Reduced tumour volume | 114 |
| Melanoma | A375 | Athymic | scFv 9.2.27-TRAIL | Reduced tumor volume | 139 |
| Melanoma | MV3 M21 |
NOD-SCID | mAb scFv-FcC21 | Reduced level of lung metastases; increased survival |
140 |
| Melanoma | A375M | NOD-SCID | MV-FCU1-αHMWMAA + 5-FC6 | Reduced tumour volume | 141 |
| Mesothelioma | PPM-Mill | C.B.17 SCID/SCID | mAb TP41.2 | Reduced tumour volume | 44 |
| AML | ML-2 | NOD-SCID | mAbs 225.28, 653.25;763.74, TP61.5, VT68.2 | No effect | 106 |
| Syngenic and/or transgenic | |||||
| Breast carcinoma/ Melanoma |
B16F10 B16F10-NG2+5 |
C57BL/6 NT-2 FVB/N HER-2/neu |
Immunization with Lm-HMW-MAA-C7 |
Impaired angiogenesis; reduced tumour volume |
142 |
| Breast carcinoma | None | MMTV-PyMT-NG2-/- | NG2/CSPG4-/- + virally induced tumors |
Delayed tumour formation; impaired angiogenesis | 124 |
| Glioblastoma | None | C57BL/6-NG2-/- C57BL/6 |
NG2/CSPG4-/- or NG2/CSPG4 miRNA + ectopic PDGF-BB8 | No effect | 49 |
| Glioblastoma/ Melanoma |
B16F10-NG2+5, CT2A | C57Bl/6-NG2-/- | NG2/CSPG4-/- | Delayed tumour growth | 121 |
| Melanoma | B16F10-NG2+5 B16F1-NG2+5 |
C57Bl/6 | NG2/CSPG4-/- | Increased tumour volume; increased metastasis formation |
92 |
| Melanoma | OCM-1A | C57BL/6-NG2-/- C57BL/6 |
NG2/CSPG4-/- + Cyclosporin A | Impaired angiogenesis; reduced tumor volume |
120 |
| Melanoma | B16F10 | C57BL/6-NG2-/- C57BL/6-NG2-/--PDGFRB-CRE9 |
Ablation of pericyte NG2/CSPG4 | Impaired angiogenesis | 143 |
| Melanoma | B16F10 | BALB/c mice | TH10-DTX-NP10 | Increased survival; impaired angiogenesis (lung metastases) | 144 |
1Reported findings refer to tumour models with constitutively high expression of NG2/CSPG4, cell lines with forced (over)expression of the PG and models of RNAi-mediated knockdown of NG2/CSPG4;
2The MDA-MB-435 cell line is recognized to be of melanoma origin and has been misquoted in Wang et al. 2010 43;
3DAVLBHY = 4-desacetylvinblastine-3-carboxyhydrazide;
4Refers to cells stably transfected with a shRNA probe to induce persistent knockdown of NG2/CSPG4;
5Refers to studies in which glioblastoma cell lines were stably transfected to overexpress NG2/CSPG4;
6Oncolytic measles virus entering melanoma cells through NG2/CSPG4 and carrying FCU1 gene encoding the yeast-derived prodrug convertases cytosine deaminase and uracil phosphoribosyltransferase for the conversion of the prodrug 5-fluorocytosine into 5-fluorouracil;
7Lm-LLO-HMW-MAA-C = Recombinant Lm(Listeria monocytogenes)-based vaccine secreting a fragment of NG2/CSPG4 fused to LLO;
8Intra-uterus injection of PDGF-BB or NG2/CSPG4-directed miRNA into E14 embryonic brains;
9NG2/CSPG4 floxed mice and PDGFR-B-Cre transgenic mice were backcrossed to a C57Bl/6 background;
10TH10-DTX-NP = TH10 peptide (TAASGVRSMH) conjugated to docetaxel-loaded nanoparticles.